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Cited by 130Antifungal resistance and susceptibilityFungal and yeast genetics researchBacterial biofilms and quorum sensing

Candida glabrata Biofilms: How Far Have We Come?

Open access
Rodrigues, Célia, Rodrigues, Maria, Silva, Sónia, Henriques, Mariana·2017·Journal of Fungi
DOI 10.3390/jof3010011PMC PMC5715960
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Abstract

Infections caused by Candida species have been increasing in the last decades and can result in local or systemic infections, with high morbidity and mortality. After Candida albicans, Candida glabrata is one of the most prevalent pathogenic fungi in humans. In addition to the high antifungal drugs resistance and inability to form hyphae or secret hydrolases, C. glabrata retain many virulence factors that contribute to its extreme aggressiveness and result in a low therapeutic response and serious recurrent candidiasis, particularly biofilm formation ability. For their extraordinary organization, especially regarding the complex structure of the matrix, biofilms are very resistant to antifungal treatments. Thus, new approaches to the treatment of C. glabrata’s biofilms are emerging. In this article, the knowledge available on C. glabrata’s resistance will be highlighted, with a special focus on biofilms, as well as new therapeutic alternatives to control them.

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes Candida glabrata biology, epidemiology, antifungal resistance mechanisms, and the role of biofilms in treatment failure. It also surveys emerging alternative therapies, including plant derivatives, honey, photodynamic therapy, and novel antifungal compounds.

Key findings

  • C. glabrata is the second most frequent Candida species after C. albicans in the USA and Canada; the European Confederation of Medical Mycology survey reported around 14% of candidiasis and 15% of Candida-related systemic bloodstream infections, and mortality associated with C. glabrata is the highest among Candida species, with 49% mortality in a retrospective series of 139 bloodstream infection cases.
  • Across geographic regions, non-susceptible or resistant clinical C. glabrata isolates were reported as: fluconazole 3.4–70%, amphotericin B 2.5–60%, caspofungin 1.3–16.2%, and 5-flucytosine 0.8–35%; echinocandin resistance increased from 4.9% to 12.3% between 2001 and 2010, and among 78 fluconazole-resistant isolates, 14.1% were resistant to one or more echinocandin and almost 8% had FKS mutations.
  • Cross-resistance is reported: 11.1–58.3% of echinocandin-resistant C. glabrata isolates had cross-resistance against fluconazole or other azoles.
  • Biofilm-associated resistance is attributed to up-regulation of efflux pumps (ABC transporters CDR1, CDR2, SNQ2; MFS; PDR1), cell wall composition, increased cell density and quorum sensing, extracellular matrix components such as β-1,3-glucans, metabolic and stress responses, and persister cells; alternative therapies reviewed include plant essential oils/extracts, honey, photodynamic therapy, novel antifungals, combination therapy, and nanoparticles.

Methods

  • Design: narrative review; no primary experimental study is presented.
  • Data or sample: synthesizes published literature on C. glabrata epidemiology, virulence, antifungal resistance, biofilms, and alternative therapies; no primary sample or dataset is analyzed.
  • Main analysis: thematic synthesis of cited studies; no systematic search strategy, meta-analysis, or primary statistical analysis is described.

Limitations

  • Stated limitations: Not stated in the paper.
  • Evident from text: as a narrative review, it does not report a systematic search strategy, inclusion/exclusion criteria, or quantitative synthesis, so conclusions depend on the cited studies.
  • Evident from text: no primary data are presented, so no new experimental validation is provided.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/jof3010011

Cites

269 of 269 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 282 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Candida glabrata retains many virulence factors that contribute to its extreme aggressiveness.

    “C. glabrata retain many virulence factors that contribute to its extreme aggressiveness and result in a low therapeutic response and serious recurrent candidiasis”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Rodrigues, 2014, Candida glabrata: A review of its features and resistance, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [39] Negri, 2012, Insights into Candida tropicalis nosocomial infections and virulence factors, Eur. J. Clin. Microbiol. Infect. Dis. source

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  • Premisecitation

    Adhesion is an extremely important step in biofilm formation and in infection processes.

    “Adhesion is an extremely important step, not only in the biofilm formation, but also in the infections processes”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Silva, 2012, Candida glabrata, Candida parapsilosis and Candida tropicalis: Biology, epidemiology, pathogenicity and antifungal resistance, FEMS Microbiol. Rev. source

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    • cites [45] Klotz, 1985, Factors Governing Adherence of Candida Species to Plastic Surfaces, Infect. Immun. source

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  • Premisecitation

    EPA1, EPA6, and EPA7 are the most important adhesins.

    “however, EPA1, EPA6, and EPA7 are the most important adhesins [49].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Castano, 2005, Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata, Mol. Microbiol. source

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  • Interpretationreasoning

    The complex structure of the biofilm matrix contributes to biofilm resistance to antifungal treatments.

    “For their extraordinary organization, especially regarding the complex structure of the matrix, biofilms are very resistant to antifungal treatments.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Candida glabrata clinical isolates have the ability to form a compact biofilm structure in different multilayers.

    “Candida glabrata clinical isolates have the ability to form a compact biofilm structure in different multilayers [40,41]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [40] Silva, 2009, Biofilms of non-Candida albicans Candida species: Quantification, structure and matrix composition, Med. Mycol. source

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    • cites [41] Fonseca, 2014, Effects of fluconazole on Candida glabrata biofilms and its relationship with ABC transporter gene expression, Biofouling source

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  • Classified as probably not a substantial claim. 17
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  • The quote only partly states this claim. 3

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    Premisecitation

    The EPA gene family is composed of 17-23 genes depending on the strain.

    “The family of EPA genes are composed of 17–23 genes depending on the strain”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Castano, 2005, Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata, Mol. Microbiol. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    After Candida albicans, Candida glabrata is one of the most prevalent pathogenic fungi in humans.

    “After Candida albicans, Candida glabrata is one of the most prevalent pathogenic fungi in humans.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Fidel, 1999, Candida glabrata: Review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans, Clin. Microbiol. Rev. source

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    • cites [10] Rodrigues, 2014, Candida glabrata: A review of its features and resistance, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [11] Colombo, 2007, Prospective observational study of candidemia in Sao Paulo, Brazil: Incidence rate, epidemiology, and predictors of mortality, Infect. Control Hosp. Epidemiol. source

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  • May combine two claims.

    Premisecitation

    Biofilms confer significant resistance to antifungal therapy and host immune responses.

    “Biofilms are known as surface-associated communities of microorganisms embedded in an extracellular matrix [42,43], which confer significant antifungal therapy and host immune responses [4,10,41].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [4] Silva, 2012, Candida glabrata, Candida parapsilosis and Candida tropicalis: Biology, epidemiology, pathogenicity and antifungal resistance, FEMS Microbiol. Rev. source

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    • cites [10] Rodrigues, 2014, Candida glabrata: A review of its features and resistance, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [41] Fonseca, 2014, Effects of fluconazole on Candida glabrata biofilms and its relationship with ABC transporter gene expression, Biofouling source

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    Premisecitation

    These secreted enzymes contribute to extreme aggressiveness resulting in a low therapeutic response and serious recurrent candidiasis.

    “that contribute towards an extreme aggressiveness resulting in a low therapeutic response and serious recurrent candidiasis [10,39].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Rodrigues, 2014, Candida glabrata: A review of its features and resistance, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [39] Negri, 2012, Insights into Candida tropicalis nosocomial infections and virulence factors, Eur. J. Clin. Microbiol. Infect. Dis. source

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    Premisecitation

    Candida glabrata and Candida krusei are intrinsically resistant to fluconazole.

    “C. glabrata and Candida krusei, which are known to be intrinsically resistant to fluconazole [23,24,26,27,28,29,30,31].”
    Quote in the paperNot a substantial claim0 of 8 sources checked
    • cites [23] Pfaller, 1998, National surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program, Diagn. Microbiol. Infect. Dis. source

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    • cites [24] Pfaller, 2000, Bloodstream infections due to Candida species: SENTRY antimicrobial surveillance program in North America and Latin America, 1997–1998, Antimicrob. Agents Chemother. source

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    • cites [26] Pfaller, 1999, International surveillance of blood stream infections due to Candida species in the European SENTRY Program: species distribution and antifungal susceptibility including the investigational triazole and echinocandin agents. SENTRY Participant Group (Euro), Diagn. Microbiol. Infect. Dis. source

      Not checked in the free run.

    • cites [27] 1999, Estudio multicéntrico sobre funguemias por levaduras en España (abril-junio de 1997). Grupo de trabajo para el estudio de las funguemias, Rev. Clin. Esp.

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    • cites [28] Pfaller, 2001, International surveillance of bloodstream infections due to Candida species: Frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY Antimicrobial Surveillance Program, J. Clin. Microbiol. source

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    • cites [29] Wingard, 1995, Importance of Candida species other than C. albicans as pathogens in oncology patients, Clin. Infect. Dis. source

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    • cites [30] Rex, 1995, Antifungal susceptibility testing of isolates from a randomized, multicenter trial of fluconazole versus amphotericin B as treatment of nonneutropenic patients with candidemia, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [31] Abbas, 2000, Candida krusei fungemia. An escalating serious infection in immunocompromised patients, Arch. Intern. Med. source

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    Premisecitation

    Candida glabrata secretes phospholipases, lipases, and haemolysins.

    “C. glabrata retain many virulence factors such as the capacity to secrete phospholipases, lipases, and haemolysins”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Rodrigues, 2014, Candida glabrata: A review of its features and resistance, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [39] Negri, 2012, Insights into Candida tropicalis nosocomial infections and virulence factors, Eur. J. Clin. Microbiol. Infect. Dis. source

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    Premisecitation

    Candida glabrata's virulence factors result in a low therapeutic response and serious recurrent candidiasis.

    “C. glabrata retain many virulence factors that contribute to its extreme aggressiveness and result in a low therapeutic response and serious recurrent candidiasis”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Rodrigues, 2014, Candida glabrata: A review of its features and resistance, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [39] Negri, 2012, Insights into Candida tropicalis nosocomial infections and virulence factors, Eur. J. Clin. Microbiol. Infect. Dis. source

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    Premisecitation

    The number of candidiasis due to non-Candida albicans Candida (NCAC) species has meaningfully increased, namely in regard to Candida glabrata strains.

    “in the last few decades, the number of candidiasis due to non-Candida albicans Candida (NCAC) species has meaningfully raised, namely in regard to C. glabrata strains [1,10,11].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Fidel, 1999, Candida glabrata: Review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans, Clin. Microbiol. Rev. source

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    • cites [10] Rodrigues, 2014, Candida glabrata: A review of its features and resistance, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [11] Colombo, 2007, Prospective observational study of candidemia in Sao Paulo, Brazil: Incidence rate, epidemiology, and predictors of mortality, Infect. Control Hosp. Epidemiol. source

      Not checked in the free run.

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    Premisecitation

    Candida glabrata is unable to form hyphae or secrete hydrolases.

    “In addition to the high antifungal drugs resistance and inability to form hyphae or secret hydrolases, C. glabrata retain many virulence factors”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Rodrigues, 2014, Candida glabrata: A review of its features and resistance, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [39] Negri, 2012, Insights into Candida tropicalis nosocomial infections and virulence factors, Eur. J. Clin. Microbiol. Infect. Dis. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Compared to other Candida species infections, the mortality rate associated with Candida glabrata is the highest.

    “compared to other Candida species infections, the mortality rate associated with C. glabrata is the highest [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Anaissie, 1997, The epidemiology of hematogeneous candidiasis caused by different Candida species, Clin. Infect. Dis. source

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    Premisecitation

    Acquired resistance of Candida glabrata to azole drugs is linked to several mechanisms, but the most common is induction of efflux pumps encoded by ABC-transporter genes (CDR1, CDR2, SNQ2) or MDR belonging to MFS, leading to decreased drug concentration.

    “The acquired resistance of C. glabrata to azole drugs is linked to several mechanisms, but the most common is the induction of efflux pumps, encoded by the ABC-transporter genes (CDR1 and CDR2, SNQ2) or to MDR belonging to the major facilitator superfamily (MFS) that lead to decreased drug concentration [90].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [90] Kanafani, 2008, Resistance to antifungal agents: mechanisms and clinical impact, Clin. Infect. Dis. source

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    Premisecitation

    Several Candida species isolates observed in vitro reflect a high-dose paradox linked to a complex network of pathways, causing slightly elevated MIC levels, in which cells appear to regain susceptibility at high levels of a drug.

    “Several Candida species isolates observed in vitro reflect a curious high-dose paradox which is being linked to a complex network of pathways, causing slightly elevated MIC levels, in which cells appear to regain susceptibility at high levels of a drug [127,128].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [127] Stevens, 2005, Studies of the paradoxical effect of caspofungin at high drug concentrations, Diagn. Microbiol. Infect. Dis. source

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    • cites [128] Chamilos, 2007, Paradoxical effect of echinocandins across candida species In vitro: Evidence for echinocandin-specific and candida species-related differences, Antimicrob. Agents Chemother. source

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    Interpretationcitation

    The gene profile of resistant isolates of Candida glabrata azoles is variable between countries and strains, although certain genes are commonly up or downregulated.

    “This study confirms that the gene profile of the resistant isolates of C. glabrata azoles is variable between countries and strains, although certain genes are commonly up or downregulated [104].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [104] Szweda, 2015, Mechanisms of azole resistance among clinical isolates of Candida glabrata in Poland, J. Med. Microbiol. source

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    Premisecitation

    Overexpression of STB5 in Candida glabrata represses azole resistance, while its deletion produces a minor intensification in resistance.

    “It was found that the overexpression of STB5 in C. glabrata represses azole resistance, while its deletion produces a minor intensification in resistance.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [91] Ferrari, S., Sanguinetti, M., Torelli, R., Posteraro, B., and Sanglard, D. (2011). Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata. PLoS ONE, 6. source

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    • cites [96] Paul, 2011, Regulation of the CGPDR1 transcription factor from the pathogen Candida glabrata, Eukaryot. Cell source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Candida glabrata has been frequently reported as exhibiting variable karyotypes between isolates.

    “C. glabrata has been frequently reported as exhibiting variable karyotypes between isolates [57,58,59,60,61,62,63,64]”
    Quote in the paperNot a substantial claim0 of 8 sources checked
    • cites [57] Shahi, 2009, Coordinate control of lipid composition and drug transport activities is required for normal multidrug resistance in fungi, Biochim. Biophys. Acta source

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    • cites [58] Muller, 2009, Genomic polymorphism in the population of Candida glabrata: gene copy-number variation and chromosomal translocations, Fungal Genet. Biol. source

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    • cites [59] Thierry, 2008, Megasatellites: a peculiar class of giant minisatellites in genes involved in cell adhesion and pathogenicity in Candida glabrata, Nucleic Acids Res. source

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    • cites [60] Barchiesi, 1999, Electrophoretic Karyotyping and Triazole Susceptibility of Candida glabrata Clinical Isolates, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [61] Kaufmann, 1989, Electrophoretic karyotypes of Torulopsis glabrata, J. Clin. Microbiol. source

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    • cites [62] Rimek, 2000, Karyotyping of Candida albicans and Candida glabrata from patients with Candida sepsis, Mycoses source

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    • cites [63] Lin, 2007, Assessment of Candida glabrata strain relatedness by pulsed-field gel electrophoresis and multilocus sequence typing, J. Clin. Microbiol. source

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    • cites [64] Shin, 2007, Changes in karyotype and azole susceptibility of sequential bloodstream isolates from patients with Candida glabrata candidemia, J. Clin. Microbiol. source

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    Premisecitation

    Among 78 fluconazole resistant isolates, 14.1% were resistant to one or more echinocandin and almost 8% had a FKS mutation (FKS1/FKS2), which appeared due to prior echinocandin therapy.

    “among the 78 fluconazole resistant isolates, 14.1% were resistant to one or more echinocandin and almost 8% of the isolates had a FKS mutation (FKS1/FKS2 mutations), which appeared due to a prior echinocandin therapy.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Alexander, 2013, Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations, Clin. Infect. Dis. source

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    Premisecitation

    Usually Candida glabrata strains are unable to express EPA6 in vitro, but it is expressed during urinary infection due to low levels of nicotinic acid.

    “usually C. glabrata strains are unable to express EPA6 in vitro, however, it is expressed during urinary infection, due to low levels of nicotinic acid [51].”
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    • cites [51] Filler, 2006, Candida–host cell receptor–ligand interactions, Curr. Opin. Microbiol. source

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    Premisecitation

    Initial attachment of Candida glabrata cells is followed by cell division, and this proliferation leads to formation of a basal layer of anchoring microcolonies, with subsequent biofilm maturation.

    “Initial attachment of C. glabrata cells is followed by cell division, and this proliferation leads to the formation of a basal layer of anchoring microcolonies, with subsequent biofilm maturation [4,44].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Silva, 2012, Candida glabrata, Candida parapsilosis and Candida tropicalis: Biology, epidemiology, pathogenicity and antifungal resistance, FEMS Microbiol. Rev. source

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    • cites [44] Rodrigues, 2016, Candida glabrata’s recurrent infections: biofilm formation during Amphotericin B treatment, Lett. Appl. Microbiol. source

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    Premisecitation

    Biofilm conditions and high cell density are adhesion inducers, activating EPA6, whereas EPA1 is triggered typically in the lag phase.

    “Biofilm conditions and high cell density are adhesion inducers, activating EPA6, whereas EPA1 is triggered typically in the lag phase”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Silva, 2012, Candida glabrata, Candida parapsilosis and Candida tropicalis: Biology, epidemiology, pathogenicity and antifungal resistance, FEMS Microbiol. Rev. source

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    • cites [54] Silva, 2011, Adherence and biofilm formation of non-Candida albicans Candida species, Trends Microbiol. source

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    Premisecitation

    Similar to all Candida species, Candida glabrata has the competence to respond to environmental alterations, allowing them to adapt to the presence of antifungal agents, thereby providing protection against antimicrobial therapies.

    “Thus, similar to all Candida species, C. glabrata have the competence to respond to environmental alterations, allowing them to adapt to the presence of antifungal agents, thereby providing protection against antimicrobial therapies [68].”
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    • cites [68] Jandric, 2011, Stress response in Candida glabrata: pieces of a fragmented picture, Futur. Mirobiology

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    There has been an epidemiological change from Candida albicans to NCAC species, with Candida glabrata and Candida krusei emerging as important and potentially antifungal resistant causes of candidaemia.

    “There has been an epidemiological change from C. albicans to NCAC species, with C. glabrata and C. krusei emerging as important and potentially antifungal resistant causes of candidaemia [56].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Cleveland, 2012, Changes in incidence and antifungal drug resistance in candidemia: Results from population-based laboratory surveillance in Atlanta and Baltimore, 2008–2011, Clin. Infect. Dis. source

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    Premisecitation

    CDR1 and CDR2 genes are expectedly upregulated in azole-resistant isolates (≥2-fold) and FAA1 gene presented ≥2-fold expression in resistant isolates, compared to susceptible isolates and reference strain.

    “A study by Farahyar et al. [97] demonstrated that CDR1 and CDR2 genes are expectedly upregulated in azole-resistant isolates (≥2-fold) and that, fatty acid activator 1 (FAA1) gene presented a ≥2-fold expression in resistant isolates, when compared to the susceptible isolates and the reference strain.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Farahyar, 2015, Expression of efflux pumps and fatty acid activator one genes in azole resistant Candida glabrata isolated from immunocompromised patients, Acta Med. Iran.

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    Premisecitation

    Complementation of this strain with a wild-type copy of the ERG6 gene regenerated susceptibility to polyenes and standard morphology.

    “The complementation of this strain with a wild-type copy of the ERG6 gene regenerated the susceptibility to polyenes and the standard morphology [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Vandeputte, 2007, Reduced susceptibility to polyenes associated with a missense mutation in the ERG6 gene in a clinical isolate of Candida glabrata with pseudohyphal growth, Antimicrob. Agents Chemother. source

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    Premisecitation

    Micafungin MIC levels of Candida glabrata FKS hot spot mutant isolates were observed to be less elevated than those obtained for the other echinocandins, showing that the efficacy of micafungin could be differentially dependent on specific FKS gene mutations.

    “Curiously, micafungin MIC levels of C. glabrata FKS hot spot mutant isolates were observed to be less elevated than those obtained for the other echinocandins, showing that the efficacy of micafungin could be differentially dependent on specific FKS gene mutations [126].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [126] Arendrup, M., Perlin, D., Jensen, R., Howard, S., Goodwin, J., and Hopec, W. (2012). Differential in vivo activities of anidulafungin, caspofungin, and micafungin against Candida glabrata isolates with and without FSK resistance mutations. Antimicrob. Agents Chemother., 2435–2442. source

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    Premisecitation

    Acquired FKS mutations confer low β-1,3-d-glucan synthase sensitivity, higher MIC values, and clinical failure.

    “acquired FKS mutations [117] which confer low β-1,3-d-glucan synthase sensitivity, higher MIC values, and clinical failure [118]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [117] Shields, 2012, The presence of an FKS mutation rather than MIC is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to Candida glabrata, Antimicrob. Agents Chemother. source

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    • cites [118] Beyda, 2012, Echinocandin resistance in Candida species: mechanisms of reduced susceptibility and therapeutic approaches, Ann. Pharmacother. source

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    Premisecitation

    Neither glucose nor iron limitation disturbs Candida species biofilm resistance to amphotericin B.

    “In another study [161], the same authors demonstrated that neither glucose nor iron limitation disturbs Candida species biofilm resistance to amphotericin B.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [161] Baillie, 1998, Iron-limited biofilms of Candida albicans and their susceptibility to amphotericin B, Antimicrob. Agents Chemother. source

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    Premisenone given

    The biofilm structure reflects the sequence of cell division events that occur during biofilm development and results in an exceptionally resistant profile of the biofilm cells to one or several antifungal drugs.

    “The biofilm structure, thus, reflects the sequence of cell division events that occur during a biofilm development and results in an exceptionally resistant profile of the biofilm cells to one or several antifungal drugs.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Disruption of β-1,3-glucans or β-1,3-glucanase treatment increases biofilm susceptibility to fluconazole, and addition of exogenous β-1,3 glucans increases fluconazole resistance in planktonic cells.

    “When induced, the disruption of β-1,3-glucans or a β-1,3-glucanase treatment have been shown to increase susceptibility of biofilms to fluconazole and the addition of exogenous β-1,3 glucans has been demonstrated to result in the rise of resistance to fluconazole in planktonic cells [155].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [155] Mitchell, 2013, Role of matrix β-1,3-glucan in antifungal resistance of non-albicans Candida biofilms, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • Rests on an assumption: β-glucans are the most important components of the Candida species biofilm matrix and are polymers of the fungal cell wall.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Resistance to chlorhexidine, fluconazole, amphotericin B, and nystatin increases as biofilms mature over time, corresponding to growth in metabolic activity over biofilm maturation.

    “A study showed that the resistance to chlorhexidine, fluconazole, amphotericin B, and nystatin increased as biofilms mature over time, corresponding to a growth in metabolic activity over biofilm maturation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [159] Chandra, 2001, Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance, J. Bacteriol. source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    In experiments on biofilm maturation and metabolic activity, cell number was not controlled, making it unclear if the result is a true demonstration of metabolic activity.

    “However, in these experiments, cell number was not controlled, thus making it unclear if this is a true demonstration of metabolic activity [159].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [159] Chandra, 2001, Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance, J. Bacteriol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Efflux pump genes are also up-regulated in mature biofilms, demonstrating that they continue to mediate drug resistance throughout biofilm development.

    “which are also up-regulated in mature biofilms, demonstrating that they continue to mediate drug resistance throughout biofilm development [141,142,143].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [141] Nobile, 2012, A recently evolved transcriptional network controls biofilm development in Candida albicans, Cell source

      Not checked in the free run.

    • cites [142] Ramage, 2002, Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms, J. Antimicrob. Chemother. source

      Not checked in the free run.

    • cites [143] Yeater, K., Chandra, J., Cheng, G., Mukherjee, P., Zhao, X., Rodriguez- Zas, S., Kwast, K., Ghannoum, M., and Hoyer, L. (2007). Temporal analysis of Candida albicans gene expression during biofilm development. Microbiology, 2373–2385. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Two main classes of efflux pumps contribute to antifungal drug resistance: the ABC transporter superfamily containing CDR1 and CDR2, and the MFS superfamily containing MDR1.

    “Two main classes of efflux pumps contribute to antifungal drug resistance: the ATP binding cassette (ABC) transporter superfamily containing CDR1 and CDR2, and the MFS superfamily containing MDR1 [130,134,135].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [130] Ramage, 2012, Fungal biofilm resistance, Int. J. Microbiol. source

      Not checked in the free run.

    • cites [134] Anderson, 2005, Evolution of antifungal-drug resistance: Mechanisms and pathogen fitness, Nat. Rev. Microbiol. source

      Not checked in the free run.

    • cites [135] Falkler, 2004, Fungal biofilms and drug resistance, Emerg. Infect. Dis. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Persister cells form a unique group inside the biofilm cell population, are formed randomly, are phenotypically dormant, highly tolerant to antifungal drugs, and are a key mechanism of resistance in chronic infections.

    “Inside the biofilm cell population, persister cells form a unique group that is formed randomly, phenotypically dormant, highly tolerant to antifungal drugs [164], and which is a key mechanism of resistance in chronic infections [130].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [164] LaFleur, 2006, Candida albicans biofilms produce antifungal-tolerant persister cells, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [130] Ramage, 2012, Fungal biofilm resistance, Int. J. Microbiol. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Another ABC transporter, PDR1, was evaluated and found to be overexpressed in Candida glabrata biofilms.

    “Similarly, another ABC transporter, PDR1, was evaluated and was found to be overexpressed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Fonseca, 2014, Effects of fluconazole on Candida glabrata biofilms and its relationship with ABC transporter gene expression, Biofouling source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    These alterations were linked to modifications in the structure of Candida glabrata biofilms by creating cell clusters, which could be a possible mechanism of biofilm tolerance to fluconazole.

    “These alterations were linked to modifications in the structure of C. glabrata biofilms by creating cell clusters, which could be a possible mechanism of biofilm tolerance to fluconazole.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Fonseca, 2014, Effects of fluconazole on Candida glabrata biofilms and its relationship with ABC transporter gene expression, Biofouling source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tpo3 appears linked to the efflux of azoles and spermine, and control of the intracellular concentration of this polyamine appears important for azole resistance.

    “Likewise, Tpo3 appears to be linked to the efflux of azoles and spermine, and the control of the intracellular concentration of this polyamine appears to be important for azole resistance [208].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [208] Costa, 2014, Candida glabrata drug:H+ antiporter CgTpo3 (ORF CAGL0I10384g): role in azole drug resistance and polyamine homeostasis, J. Antimicrob. Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Gal11/Med15 KIX domain is involved in Pdr1 orthologues and in the clinically important C. glabrata multidrug resistance.

    “This Gal11/Med15 KIX domain is involved in Pdr1 orthologues and in the clinically important C. glabrata multidrug resistance pathogenenis [205].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [205] Paul, 2014, Multidrug resistance in fungi: Regulation of transporter-encoding gene expression, Front. Physiol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Estimates of non-susceptible or resistant C. glabrata clinical isolates across several geographic regions are: fluconazole 3.4%-70%, amphotericin B 2.5%-60%, caspofungin 1.3%-16.2%, and 5-flucytosine 0.8%-35%.

    “Estimates regarding the percentage of non-susceptible or resistant C. glabrata clinical isolates against four antifungal drugs used in clinical practice, across several geographic regions are: fluconazole, 3.4%–70%; amphotericin B, 2.5%–60%; caspofungin, 1.3%–16.2%, and 5-flucytosine, 0.8%–35%, which are clearly concerning numbers [171,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [171] Sadeghi, 2014, Species distribution and antifungal susceptibility of Candida spp. isolated from superficial Candidiasis in outpatients in Iran, J. Mycol. Med. source

      Not checked in the free run.

    • cites [173] Farmakiotis, 2014, Drug-resistant Candida glabrata infection in cancer patients, Emerg. Infect. Dis. source

      Not checked in the free run.

    • cites [174] Mohamadi, 2014, Anti-fungal resistance in candida isolated from oral and diaper rash Candidiasis in neonates, Bioinformation source

      Not checked in the free run.

    • cites [175] Nieto, 2015, Sentinel surveillance of invasive candidiasis in Spain: Epidemiology and antifungal susceptibility, Diagn. Microbiol. Infect. Dis. source

      Not checked in the free run.

    • cites [176] Pfaller, 2015, Isavuconazole, micafungin, and 8 comparator antifungal agents’ susceptibility profiles for common and uncommon opportunistic fungi collected in 2013: temporal analysis of antifungal drug resistance using CLSI species-specific clinical breakpoints and proposed epidemiological cutoff values, Diagn. Microbiol. Infect. Dis. source

      Not checked in the free run.

    • cites [177] Schmalreck, 2012, Antifungal Susceptibility Testing-AFST Study Group Species and susceptibility distribution of 1062 clinical yeast isolates to azoles, echinocandins, flucytosine and amphotericin B from a multi-centre study, Mycoses source

      Not checked in the free run.

    • cites [178] Shi, 2015, Molecular identification and antifungal susceptibility of 186 Candida isolates from vulvovaginal Candidiasis in Southern China, J. Med. Microbiol. source

      Not checked in the free run.

    • cites [179] Zarei Mahmoudabadi, A., Rezaei-Matehkolaei, A., and Ghanavati, F. (2015). The Susceptibility Patterns of Candida Species Isolated From Urine Samples to Posaconazole and Caspofungin. Jundishapur J. Microbiol., 8. source

      Not checked in the free run.

    • cites [180] Posteraro, 2015, Antifungal susceptibility profiles of bloodstream yeast isolates by sensititre yeastone over nine years at a large Italian teaching hospital, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [181] Czaika, 2014, Detection of azole susceptibility patterns in clinical yeast strains isolated from 1998 to 2008, New Microbiol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pdr1 and CDR1 mediated the fluconazole resistance phenotype of Δhst1 cells, while the transcriptional activator Msn4 and the catalase Cta1 were required to provide oxidative stress resistance.

    “Pdr1 and CDR1 mediated the fluconazole resistance phenotype of the Δ hst1 cells, while the transcriptional activator Msn4 and the catalase Cta1 were required to provide oxidative stress resistance.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [206] 2013, Local silencing controls the oxidative stress response and the multidrug resistance in Candida glabrata, Mol. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ras1, ras2, and tor1 mutants had a high-persister phenotype compared to wild-type biofilm and planktonic cells exposed to rapamycin, and TORC1 inhibition with rapamycin improved the proportion of persisters in C. glabrata.

    “The ras1, ras2, and tor1 mutants had a high-persister phenotype compared to wild-type biofilm and planktonic cells exposed to the TORC1 pathway inhibitor rapamycin, and, on the other hand, the inhibition of TORC1 with rapamycin similarly improved the proportion of persisters in C. glabrata.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [167] Bojsen, 2016, A common mechanism involving the TORC1 pathway can lead to amphotericin B-persistence in biofilm and planktonic Saccharomyces cerevisiae populations, Sci. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tpo3 is linked to resistance to both imidazoles and triazoles and to the polyamine spermine, and TPO3 is upregulated in C. glabrata cells exposed to spermine in a Pdr1-dependent manner.

    “The second was demonstrated to be linked to the resistance to both imidazoles and triazoles (e.g., fluconazole), and to the polyamine spermine, found in high concentrations in the urogenital tract. The authors also found that TPO3 was upregulated in C. glabrata cells exposed to spermine, in a Pdr1-dependent manner [198].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [198] Costa, C., Pais, P., and Teixeira, M.C. (2015). The Battle Against Microbial Pathogens: Basic Science, Technological Advances and Educational Programs, Formatex.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    iKIX1 inhibits Pdr1-dependent gene activation and re-sensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models for disseminated and urinary tract C. glabrata infection.

    “Results showed that iKIX1 inhibits Pdr1-dependent gene activation and re-sensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models for disseminated and urinary tract C. glabrata infection [204].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [204] Nishikawa, 2016, Inhibiting fungal multidrug resistance by disrupting an activator-Mediator interaction, Nature source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The genetic mechanism involved in this process supports the acquisition of resistance to multiple antifungals, partially explaining the higher rates of triazole and multidrug resistance associated with C. glabrata.

    “The genetic mechanism involved in this process supports the acquisition of resistance to multiple antifungals, partially explaining the higher rates of triazole and multidrug resistance associated with C. glabrata [201].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [201] Healey, 2016, Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance, Nat. Commun. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In most cases, multidrug resistance depends on the activity of ABC transporters and MFS, which are regulated by Pdr1, the major regulator of multidrug resistance in C. glabrata.

    “Not in all cases, but in most of them, this multidrug resistance phenomenon depends on the activity of ABC transporters and MFS [198], which are known to be regulated by the Pdr1 transcription factor, which is recognized to be the major regulator of multidrug resistance in C. glabrata [94].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [198] Costa, C., Pais, P., and Teixeira, M.C. (2015). The Battle Against Microbial Pathogens: Basic Science, Technological Advances and Educational Programs, Formatex.

      Not checked in the free run.

    • cites [94] Vermitsky, 2004, Azole Resistance in Candida glabrata: Coordinate upregulation of multidrug transporters and evidence for a PDR1-like transcription factor, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • Rests on an assumption: C. glabrata expresses three ABC transporters: CDR1, CDR2, and SNQ2.

  • May combine two claims.

    Premisecitation

    The transcription factor Sum1 interacts with Hst1 and participates in the regulation of these genes.

    “Also, the authors showed that the transcription factor Sum1 interacts with Hst1 and participates in the regulation of these genes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [206] 2013, Local silencing controls the oxidative stress response and the multidrug resistance in Candida glabrata, Mol. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Deletion of CDR1 in an azole-resistant strain leads to intracellular accumulation of fluconazole and hypersusceptibility to other azoles, and additional CDR2 deletion worsens this phenotype.

    “Studies revealed that the deletion of CDR1 in an azole-resistant strain leads to the intracellular accumulation of fluconazole and hypersusceptibility to other azoles. The additional CDR2 deletion worsens this phenotype [91,199].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [91] Ferrari, S., Sanguinetti, M., Torelli, R., Posteraro, B., and Sanglard, D. (2011). Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata. PLoS ONE, 6. source

      Not checked in the free run.

    • cites [199] Sanglard, 2001, Role of ATP-binding-cassette transporter genes in high-frequency acquisition of resistance to azole antifungals in Candida glabrata, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • Rests on an assumption: C. glabrata expresses three ABC transporters: CDR1, CDR2, and SNQ2.

  • May combine two claims.

    Premisecitation

    Qdr2 is a cause of resistance to imidazoles and plays an active part in the efflux of these drugs, and its expression is stimulated in clotrimazole-stressed cells under Pdr1 control.

    “The first was acknowledged to be a cause of resistance to imidazoles (e.g., clotrimazole, miconazole, tioconazole, and ketoconazole) and was proven to play an active part in the efflux of these drugs. Its expression was found to be stimulated in clotrimazole-stressed cells, under Pdr1 control [207].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [207] Costa, 2013, Candida glabrata drug:H+ antiporter CgQdr2 confers imidazole drug resistance, being activated by transcription factor CgPdr1, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Multiple antifungal resistance and cross-resistance among more than one class of antifungal drugs is growing in clinical isolates.

    “Studies with clinical isolates obtained from patients in several epidemiological studies show that not only has multiple antifungal resistance been described in isolated events, but also that cross-resistance among more than one class of antifungal drugs is growing [171].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [171] Sadeghi, 2014, Species distribution and antifungal susceptibility of Candida spp. isolated from superficial Candidiasis in outpatients in Iran, J. Mycol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Candida species persister cells are exclusively recovered from biofilms and not from planktonic populations, notwithstanding growth phase, and involve attachment to a substrate to initiate the dormant phenotype.

    “Candida species persister cells are exclusively recovered from biofilms and not from planktonic populations, notwithstanding their growth phase, and involve attachment to a substrate to initiate the dormant phenotype.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Other cases of induced cross-resistance to azole drugs in C. glabrata were related to resistance against both azoles and amphotericin B and to prochloraz.

    “Other cases of induced cross-resistance to azole drugs in C. glabrata were related to resistance against both azoles and amphotericin B [198,199,212] and related to prochloraz (an agricultural antifungal).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [198] Costa, C., Pais, P., and Teixeira, M.C. (2015). The Battle Against Microbial Pathogens: Basic Science, Technological Advances and Educational Programs, Formatex.

      Not checked in the free run.

    • cites [199] Sanglard, 2001, Role of ATP-binding-cassette transporter genes in high-frequency acquisition of resistance to azole antifungals in Candida glabrata, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [212] Ferrari, S., Ischer, F., Calabrese, D., Posteraro, B., Sanguinetti, M., Fadda, G., Rohde, B., Bauser, C., Bader, O., and Sanglard, D. (2009). Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog., 5. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is limited information about the mechanism of action of photodynamic approaches for specific pathogens as well as the risks to healthy tissues.

    “Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about their mechanism of action for specific pathogens as well as the risks to healthy tissues [260].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [260] Martinez, 2015, Antimicrobial photodynamic therapy: an effective alternative approach to control fungal infections, Front. Microbiol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Mirtus communis leaf and flower extracts are rich in tannins while the stem is rich in flavonoids.

    “For example, Mirtus communis L. (myrtle) leaf and flower extracts are rich in tannins while the stem is rich in flavonoids [237].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [237] Mhamdi, 2010, Antioxidant activities of the essential oils and methanol extracts from myrtle (Myrtus communis var. Italica L.) leaf, stem and flower, Food Chem. Toxicol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Irish et al. found that C. dubliniensis was the most susceptible species to the activity of honey, while C. glabrata was the least susceptible.

    “They found that C. dubliniensis was the most susceptible species to the activity of honey, while C. glabrata was the least susceptible.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [250] Irish, 2006, Honey has an antifungal effect against Candida species, Med. Mycol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several plant secondary metabolites such as tannins, terpenoids, alkaloids, flavonoids, and glycosides have been found to have antimicrobial properties in vitro.

    “Several plant secondary metabolites such as tannins, terpenoids, alkaloids, flavonoids, and glycosides have been found to have antimicrobial properties in vitro [226,227].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [226] Dahanukar, 2000, Pharmacology of medicinal plants and natural products, Indian J. Pharmacol.

      Not checked in the free run.

    • cites [227] Cowan, 1999, Plant Products as Antimicrobial Agents, Clin. Microbiol. Rev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Flr1 is involved in resistance to benomyl, but no connection was found between this transporter and antifungal resistance.

    “Also in C. glabrata, Flr1 has been proven to be involved in the resistance of benomyl (a pesticide used in agriculture), but no connection was found between this transporter and antifungal resistance [108].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Chen, 2007, The bZip transcription factor CGAP1P is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata, Gene source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Aqr1 is an antifungal drug resistance determinant and may play an essential part in C. glabrata persistent colonization and multidrug resistance.

    “Therefore, Costa et al. [209] showed that Aqr1 is an antifungal drug resistance determinant and it may play an essential part in C. glabrata persistent colonization and multidrug resistance.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [209] Costa, 2013, The dual role of Candida glabrata drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g) in antifungal drug and acetic acid resistance, Front. Microbiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The composition of plant extracts is variable according to the solvent used for extract preparation.

    “Furthermore, the composition of the extracts is also variable according to the solvent used for extract preparation [238].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [238] Lapornik, 2005, Comparison of extracts prepared from plant by-products using different solvents and extraction time, J. Food Eng. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. glabrata is a Crabtree-positive fungus, and its respiration could be negatively affected by certain levels of glucose.

    “Moreover, C. glabrata is a Crabtree-positive fungus [220], thus its respiration could be negatively affected by certain levels of glucose [221].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [220] Tsai, 1998, Human salivary histatins: promising antifungal therapeutic agents, Crit. Rev. Oral Biol. Med. source

      Not checked in the free run.

    • cites [221] Voll, 1990, Transient-state analysis of metabolic fluxes in Crabtree-positive and Crabtreenegative yeasts, Appl. Environ. Microbiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Medicinal plants have been used since ancient times for therapeutic purposes, and superficial candidiasis is traditionally treated with topical application of calendula and commiphora.

    “Medicinal plants have been used since ancient times for therapeutic purposes. For example, superficial candidiasis is traditionally treated with a topical application of calendula and commiphora [222].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [222] Dalirsani, 2011, In vitro comparison of inhibitory activity of 10 plant extracts against Candida albicans, Aust. J. Basic Appl. Sci.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    The altered cellular sterol composition of CG156 may affect intracellular signalling and trafficking pathways, the efflux machinery, and transport proteins proposed to mediate azole import via facilitated diffusion.

    “The authors also indicate that the altered cellular sterol composition of CG156 may affect intracellular signalling and trafficking pathways, as the efflux machinery [199,211,212] and any transport proteins that are proposed to mediate azole import via facilitated diffusion [213].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [199] Sanglard, 2001, Role of ATP-binding-cassette transporter genes in high-frequency acquisition of resistance to azole antifungals in Candida glabrata, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [211] Brun, 2004, Mechanisms of azole resistance in petite mutants of Candida glabrata, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [212] Ferrari, S., Ischer, F., Calabrese, D., Posteraro, B., Sanguinetti, M., Fadda, G., Rohde, B., Bauser, C., Bader, O., and Sanglard, D. (2009). Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog., 5. source

      Not checked in the free run.

    • cites [213] Mansfield, B.E., Oltean, H.N., Oliver, B.G., Hoot, S.J., Leyde, S.E., Hedstrom, L., White, T.C., and BE, M. (2010). Azole drugs are imported by facilitated diffusion in Candida albicans and other pathogenic fungi. PLoS Pathog., 6. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Some clinical isolates might persist as slow-growing agents of chronic infections because they can survive without sterol auxotrophy, possess mutated Erg11, lack cellular ergosterol, and can opportunistically exploit a wide spectrum of host/environmental sterols for growth.

    “The results therefore indicate that some clinical isolates might persist as slow-growing agents of chronic infections, possibly since they can survive without sterol auxotrophy; possess mutated Erg11; lack cellular ergosterol (high-level resistance to polyenes); and can opportunistically exploit a wide spectrum of host/environmental sterols for growth.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [210] Hull, 2012, Facultative sterol uptake in an ergosterol-deficient clinical isolate of Candida glabrata harboring a missense mutation in ERG11 and exhibiting cross-resistance to azoles and amphotericin B, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Terbinafine treatment presented upregulation of ERG11 but had minimal effect on CDR1 and PDH1.

    “Vermitsky and colleagues [94] showed that treatment with terbinafine (allylamines antifungal class), which targets the enzyme squalene epoxidase in the ergosterol biosynthetic pathway, presented upregulation on ERG11 as previously reported, however, unlike the azoles, this drug had minimal effect on CDR1 and PDH1.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [94] Vermitsky, 2004, Azole Resistance in Candida glabrata: Coordinate upregulation of multidrug transporters and evidence for a PDR1-like transcription factor, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CG156 was found to be a low-efflux isolate; when grown on sterol-supplemented medium, its cultures reached higher cell densities with shorter lag phases, and showed variations in cellular sterol composition that did not affect its azole-resistant phenotype.

    “In this work, CG156 was found to be a low-efflux isolate and when grown on sterol-supplemented, its cultures reached higher cell densities, with shorter lag phases, and showed variations in cellular sterol composition that did not affect its azole-resistant phenotype.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [210] Hull, 2012, Facultative sterol uptake in an ergosterol-deficient clinical isolate of Candida glabrata harboring a missense mutation in ERG11 and exhibiting cross-resistance to azoles and amphotericin B, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Studies have reported bactericidal, bacteriostatic, antiviral, antioxidant, anti-inflammatory, and anti-tumoral properties of honey.

    “In fact, studies have reported the bactericidal, bacteriostatic, antiviral, antioxidant, anti-inflammatory, and anti-tumoral properties of honey [244,245,246,247].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [244] Estevinho, 2008, Antioxidant and antimicrobial effects of phenolic compounds extracts of Northeast Portugal honey, Food Chem. Toxicol. source

      Not checked in the free run.

    • cites [245] Bardy, 2008, A systematic review of honey uses and its potential value within oncology care, J. Clin. Nurs. source

      Not checked in the free run.

    • cites [246] Lusby, 2005, Bactericidal Activity of Different Honeys against Pathogenic Bacteria, Arch. Med. Res. source

      Not checked in the free run.

    • cites [247] Molan, 2001, Why honey is effective as a medicine, Bee World source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Histatins have been found to have effectiveness against diverse fungi.

    “Several studies with histatins have been performed, since these salivary cationic proteins had been found to have effectiveness against diverse fungi [215,216,217,218,219].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [215] Helmerhorst, E., Venuleo, C., Sanglard, D., and Oppenheim, F. (2006). Roles of cellular respiration, CgCDR1, and CgCDR2 in Candida glabrata resistance to histatin. Antimicrob. Agents Chemother., 1100–1103. source

      Not checked in the free run.

    • cites [216] Edgerton, 2000, Salivary histatin 5 and its similarities to the other antimicrobial proteins in human saliva, Adv. Dent. Res. source

      Not checked in the free run.

    • cites [217] Hancock, R., and Devine, D. (2004). Mammalian Antimicrobial Proteins, Cambridge University Press.

      Not checked in the free run.

    • cites [218] Tenovuo, J. (1989). Human Saliva: Clinical Chemistry and Microbiology, CRC Press.

      Not checked in the free run.

    • cites [219] Oppenheim, 1988, Histatins, a novel family of histidinerich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans, J. Biol. Chem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AQR1 deletion had no effect on the intracellular accumulation of 14C-acetic acid, suggesting that its role in acetic acid resistance may be indirect.

    “When an AQR1 deletion was performed, no effect could be noticed on the intracellular accumulation of 14C-acetic acid, thus suggesting that its role in acetic acid resistance may be indirect, possibly through the transport of a so far undisclosed physiological substrate.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [209] Costa, 2013, The dual role of Candida glabrata drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g) in antifungal drug and acetic acid resistance, Front. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Glycyrrhiza glabra extracts demonstrated anti-biofilm activity against C. tropicalis and C. glabrata, although a double concentration of extract was generally required to obtain an antifungal effect in biofilm similar to that of planktonic cells.

    “These extracts have also demonstrated anti-biofilm activity against the two Candida species, although a double concentration of extract was generally required to obtain an antifungal effect in biofilm similar to that of planktonic cells [241].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [241] Martins, 2016, In vitro anti-Candida activity of Glycyrrhiza glabra L., Ind. Crops Prod. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Antimicrobial activity against C. glabrata isolates was observed for Origanum vulgare, Lippia graveolens, and Cinnamomum zeylanicum essential oils, with the first two more active against fluconazole-susceptible C. glabrata and the latter showing the best antifungal activity against fluconazole-resistant C. glabrata isolates.

    “Antimicrobial activity against C. glabrata isolates was observed for Origanum vulgare, Lippia graveolens, and Cinnamomum zeylanicum essential oils, with the first two being more active against fluconazole-susceptible C. glabrata, and the latter showing the best antifungal activity against the fluconazole-resistant C. glabrata isolates [239].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [239] Pozzatti, 2008, In vitro activity of essential oils extracted from plants used as spices against fluconazole-resistant and fluconazole-susceptible Candida spp. Canadian, Can. J. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When CG156 was grown in the presence of ergosterol, it showed increased sensitivity to the polyene, and when grown with cholesterol it became more resistant.

    “When this isolate was grown in the presence of ergosterol, it showed increased sensitivity to the polyene and when grown with cholesterol it became more resistant.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [210] Hull, 2012, Facultative sterol uptake in an ergosterol-deficient clinical isolate of Candida glabrata harboring a missense mutation in ERG11 and exhibiting cross-resistance to azoles and amphotericin B, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vartak et al. isolated a new polyene macrolide antibiotic from Streptomyces species and found it to be specifically active against fungi, being unable to inhibit bacterial growth.

    “For example, Vartak et al. [263] isolated a new polyene macrolide antibiotic from the fermentation broth of Streptomyces species. After purification, they evaluated the antimicrobial activity against several fungi (Aspergillus fumigatus, C. albicans, C. krusei, C. glabrata, Cryptococcus neoformans, Trichophyton species, and fluconazole-resistant C. krusei and C. glabrata strains) and Gram-positive”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [263] Vartak, 2014, Isolation of a new broad spectrum antifungal polyene from Streptomyces sp. MTCC 5680, Lett. Appl. Microbiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The incidence of single, cross, and multidrug antifungal resistance within Candida glabrata strains has risen quickly.

    “The quick rise in the incidence of single, cross, and multidrug antifungal resistance within C. glabrata strains make it crucial to further increase the data on the virulence and resistance mechanisms associated with this species.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Organisms resistant to conventional antifungal agents may be successfully killed by PDT and the development of resistance to this therapy seems unlikely.

    “As a consequence of the use of non-specific oxidizing agents, organisms resistant to conventional antifungal agents may be successfully killed by PDT and the development of resistance to this therapy seems unlikely, making this a very promising therapy [257].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [257] Pavarina, 2010, Susceptibility of Candida albicans to photodynamic therapy in a murine model of oral candidosis, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cerium activity appears to result from severe cellular metabolic activity impairment and membrane damage; it prevents biofilm formation in vitro and in vivo in polyurethane catheters in mouse models and almost eradicates established biofilms at high concentrations.

    “Silva-Dias et al. [269] evaluated the antifungal properties of cerium, a lanthanide member, against planktonic and sessile Candida cells. The activity of cerium appears to result from severe cellular metabolic activity impairment and membrane damage. This compound was shown to effectively prevent biofilm formation both in vitro and in vivo in segments of polyurethane catheters in mouse models, and”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [269] Miranda, 2014, In vitro antifungal activity and in vivo antibiofilm activity of cerium nitrate against Candida species, J. Antimicrob. Chemother.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dovigo et al. observed that the fungicidal effect of PDT was strain-dependent, with significant decreases in biofilm viability for three strains of C. albicans and two strains of C. glabrata, and single-species biofilms were less susceptible to PDT than their planktonic counterparts.

    “Dovigo et al. [262] observed that the fungicidal effect of PDT was strain-dependent. Significant decreases in biofilm viability were observed for three strains of C. albicans and for two strains of C. glabrata. Moreover, single-species biofilms were less susceptible to PDT than their planktonic counterparts.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [262] Dovigo, 2011, Fungicidal effect of photodynamic therapy against fluconazole-resistant Candida albicans and Candida glabrata, Mycoses source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    One modified glucoside showed fungistatic activity threefold higher than fluconazole and fungicidal activity against C. glabrata.

    “One of the modified glucosides showed promising results, with fungistatic (threefold higher than fluconazole) and fungicidal activity against C. glabrata.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [264] Silva, 2015, New eugenol glucoside-based derivative shows fungistatic and fungicidal activity against opportunistic Candida glabrata, Chem. Biol. Drug Des.

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Raman et al. found C. tropicalis most susceptible to the β-peptide and C. glabrata least susceptible; β-peptides are mostly ineffective at disrupting Candida species biofilms but can prevent formation of C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis biofilms.

    “Raman et al. [268] evaluated the activity of amphiphilic, helical β-peptide structural mimetics of natural antimicrobial α-peptides against clinically isolated and drug resistant Candida strains. Candida tropicalis was the most susceptible to the activity of the β-peptide, while C. glabrata was the least susceptible. Interestingly, they report that β-peptides are mostly ineffective at disrupting”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [268] Raman, 2015, Antifungal Activity of 14-Helical β-peptides against planktonic cells and biofilms of Candida species, Pharmaceuticals source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Perera et al. encapsulated citric acid into a Mg-Al-layered double hydroxide; the nanoparticles in a body cream demonstrated prolonged slow release up to 8 h and improved antifungal activity against C. albicans and C. glabrata, but not C. tropicalis.

    “For example, Perera et al. [272] evaluated the encapsulation of citric acid into a Mg-Al-layered double hydroxide (LDH). Citric acid has antifungal properties and its encapsulation would allow its slow release in topical skin formulations. The nanoparticles obtained were introduced into a body cream formulation, which demonstrated a prolonged slow release up to 8 h in aqueous medium under”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [272] Perera, 2015, Slow release anti-fungal skin formulations based on citric acid intercalated layered double hydroxides nanohybrids, Chem. Cent. J. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The capacity to form biofilms is one of the most important features in Candida species pathogenicity.

    “Also, the capacity to form biofilms is one of the most important features in Candida species pathogenicity, creating a dangerous prospect of ineffective therapies against these infections.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Chloramphenicol antifungal activity was comparable to caspofungin acetate, ketoconazole, and metronidazole, but it had no activity against most C. albicans tested, C. famata, C. glabrata, C. haemolonei, and Cryptococcus neoformans.

    “The antifungal activity of chloramphenicol was comparable to other known antifungal compounds (e.g., caspofungin acetate, ketoconazole, and metronidazole). However, it had no activity against most C. albicans tested, as well as C. famata, C. glabrata, C. haemolonei and Cryptococcus neoformans.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [270] Joseph, 2015, In vitro anti-yeast activity of chloramphenicol: A preliminary report, J. Med. Mycol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A Pseudallescheria boydii strain isolated from Nasutitermes species produces tyroscherin and N-methyltyroscherin, which are effective antifungal agents with favourable selectivity indices for C. albicans and C. parapsilosis.

    “Nirma et al. [275] reported the discovery of a Pseudallescheria boydii strain isolated from Nasutitermes species The microbial symbiont produces two metabolites with antifungal activity: tyroscherin and N-methyltyroscherin, shown to be effective antifungal agents with favourable selectivity indices for C. albicans and C. parapsilosis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [275] Nirma, 2013, Antifungal Agents from Pseudallescheria boydii SNB-CN73 Isolated from a Nasutitermes sp. Termite, J. Nat. Prod. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Three active fungal extracts were fractionated into eight compounds that exhibited antifungal and cytotoxic potential against C. albicans ATCC10213.

    “Three active fungal extracts were fractionated, resulting in the isolation of eight compounds, which exhibited antifungal and cytotoxic potential against C. albicans ATCC10213.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [274] Casella, 2013, Antimicrobial and cytotoxic secondary metabolites from tropical leaf endophytes: Isolation of antibacterial agent pyrrocidine C from Lewia infectoria SNB-GTC2402, Phytochemistry source

      Not checked in the free run.

81 of 81

  • The authors state this as an assumption.

    The cell surface of Candida glabrata cells exhibits a degree of hydrophobicity comparable with Candida albicans.

    “Despite the lack of studies concerning this issue, it is assumed that the cell surface of C. glabrata cells reportedly exhibit a degree of hydrophobicity comparable with C. albicans [46].”

  • The paper relies on this without support.

    β-glucans are the most important components of the Candida species biofilm matrix and are polymers of the fungal cell wall.

    “The most important components are the β-glucans, which are polymers of the fungal cell wall and are a substantial constituent of the biofilm Candida species matrix.”

  • The paper relies on this without support.

    Alterations in temperature or specific nutrients, restricted nutrient availability, ionic stress, and variations in osmolality and oxidative stress are antifungal resistance mechanisms of biofilms.

    “Alterations in temperature or specific nutrients, restricted nutrient availability, ionic stress, and variations in osmolality and oxidative stress are all acknowledged as antifungal resistance mechanisms of biofilms.”

  • The paper relies on this without support.

    The sirtuins Sir2 and Hst1 control the expression of several genes including adhesins required for host colonization and niacin transporters needed for growth in C. glabrata.

    “The sirtuins Sir2 and Hst1 control the expression of several genes including adhesins required for host colonization and niacin transporters needed for growth in C. glabrata.”

  • The paper relies on this without support.

    Candida species tolerates stress induced by weak acids, which is a key factor in their persistence and virulence in antifungal drugs.

    “Candida species seems to tolerate stress induced by weak acids, which appears to be a key factor in their persistence and virulence in antifungal drugs.”

  • The paper relies on this without support.

    Plant antifungal properties are less explored than antibacterial properties but are thought to derive from the same secondary metabolites.

    “Plant antifungal properties are less explored than antibacterial properties, but they are thought to derive from the same secondary metabolites.”

  • The paper relies on this without support.

    C. glabrata expresses three ABC transporters: CDR1, CDR2, and SNQ2.

    “As previously explained, C. glabrata expresses three ABC transporters (CDR1, CDR2, and SNQ2).”

  • The paper relies on this without support.

    These antifungals act synergistically with acetic acid against C. glabrata.

    “It is known that these antifungals act synergistically with acetic acid against this pathogen.”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • An enhanced capacity to form biofilms can result in the acquisition of resistance, as biofilms promote yeast survival upon exposure to the drug.

    “In this regard, an enhanced capacity to form biofilms can result in the acquisition of resistance, as these structures promote yeast survival upon exposure to the drug [12,13].”

    From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [13]

  • Acquired resistance to azoles appears to be a result of mutations selected by the pressure exerted by the drug, and the adaptation is said to appear gradually during continuous contact with the antifungal.

    “Acquired resistance to this group of antimycotics seems to be a result of mutations selected by the pressure exerted by the drug [13]. The adaptation is said to appear gradually during continuous contact with the antifungal [13].”

    From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [13]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • PDR1 is identified as both a transporter and a transcription factor

    Minor

    The biofilm section calls PDR1 an ABC transporter, whereas the azole-resistance section identifies Pdr1 as a transcription factor that regulates ABC transporter genes.

1 of 1

Cites

Flagged first, then by citations

1 of the 270 references couldn’t be matched to a known paper.

Research works printed but not linked: 10

  1. Calderone, R. (2002). Candida and Candidiasis, ASM Press.
  2. Larone, H. (2002). Medically Important Fungi: A Guide to Identification, ASM Press. [4th ed.].
  3. 1999, Estudio multicéntrico sobre funguemias por levaduras en España (abril-junio de 1997). Grupo de trabajo para el estudio de las funguemias, Rev. Clin. Esp., 199, 356
  4. Wall, 1995, Trends in antifungal use and antifungal isolates in a university hospital 1990–1992, J. Hosp. Infect., 31, 149
  5. Coste, A., and Vandeputte, P. (2015). Antifungals from Genomics to Resistance and the Development of Novel Agents, Caister Academic Press.
  6. Hancock, R., and Devine, D. (2004). Mammalian Antimicrobial Proteins, Cambridge University Press.
  7. Tenovuo, J. (1989). Human Saliva: Clinical Chemistry and Microbiology, CRC Press.
  8. Ormancey, 2001, Formulation of essential oils in functional parfumery, Parfum. Cosmet. Actual., 157, 30
  9. Sharanappa, 2013, Anti-Candida activity of medicinal plants. A review, Int. J. Pharm. Pharm. Sci., 5, 9
  10. Bowles, J.E. (2003). The Chemistry of Aromatherapeutic Oils, Griffin Press. [3rd ed.].

Cited by

Sorted by citations

Related

Authors
Rodrigues, C., Rodrigues, M., Silva, S., & Henriques, M.
Affiliations
  • CEB, Centre of Biological Engineering, LIBRO—Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, 4710-057 Braga, Portugal
  • University of Minho (PT)
ORCID
Venue
Journal of Fungi
Publisher
MDPI AG
Published
2017-03-01
Volume
3
Issue
1
Pages
11
ISSN
2309-608X (ISSN-L)
DOI
10.3390/jof3010011
PMC
PMC5715960
OpenAlex
W2592604332
Semantic Scholar
85dba080d5703c74cd2f1bf8486ed22e45b777f7
Cited by
129
References
270
Citations by year
2026: 10 · 2025: 12 · 2024: 15 · 2023: 13 · 2022: 10 · 2021: 15 · 2020: 20 · 2019: 16 · 2018: 15 · 2017: 3
FWCI
2.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Fungi (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Funders
Fundação para a Ciência e a Tecnologia (COMPETE, PTDC/SAU-MIC/119069/2010, RECI/EBB-EBI/0179/2012, FCT PTDC/SAU-MIC/119069/2010, SFRH/BD/93078/2013, PEst-OE/EQB/LA0023/2013)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Keywords
Candida glabrata, biofilm, antifungal resistance, virulence factors, recurrent candidiasis, antifungal therapy, fungal infection, biofilm matrix

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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