CoChat
Sign Up
Cited by 170Antifungal resistance and susceptibilityFungal and yeast genetics researchYeasts and Rust Fungi Studies

Candida glabrata: pathogenicity and resistance mechanisms for adaptation and survival

Open access
Hassan, Yahaya, Chew, Shu Yih, Than, Leslie Thian Lung·2021·Journal of Fungi
DOI 10.3390/jof7080667PMC PMC8398317

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetic patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. This work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to susceptible host surfaces, evading host defences, replicative ageing, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, resistance to neutrophil killings, and development of resistance to antifungal drugs, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes virulence and antifungal resistance mechanisms that enable *Candida glabrata* to colonize, evade host immunity, and survive therapy. It highlights adhesion, biofilm formation, stress adaptation, replicative ageing, iron acquisition, and azole/echinocandin resistance as key contributors to its clinical persistence.

Key findings

  • *C. glabrata* is the second most frequently isolated *Candida* species in invasive candidiasis after *C. albicans*, accounting for approximately 15–25% of invasive clinical cases; invasive candidiasis due to *C. glabrata* has an estimated morbidity and mortality of approximately 40–60%.
  • Virulence factors include hydrolytic enzymes (phospholipases, proteases, haemolysins), epithelial adhesin (EPA)-family adhesins, sparse yeast-cell biofilms, cell wall/chitin remodeling, iron acquisition, environmental stress adaptation, and replicative ageing; *C. glabrata* lacks hyphal formation and provokes a weaker host immune response than *C. albicans*.
  • Resistance mechanisms include intrinsic and acquired fluconazole resistance, azole resistance via *ERG11* mutations, *PDR1* gain-of-function mutations, efflux pumps, aneuploidy, and mitochondrial dysfunction; echinocandin resistance is around 4% in *C. glabrata* and less than 1% in *C. albicans*, primarily through *FKS1* and *FKS2* hotspot mutations.
  • Biofilm formation on medical devices contributes to drug tolerance, and the review states that an estimated 65% of all human infections are of biofilm aetiology.

Methods

  • Narrative review of published research articles related to *C. glabrata* pathogenicity, retrieved from four credible databases: Google Scholar, ScienceDirect, PubMed, and Scopus.
  • The paper synthesizes cited studies on virulence factors, host–pathogen interactions, and antifungal resistance mechanisms; it reports no primary experiments or new data.
  • No systematic search dates, inclusion/exclusion criteria, or quality appraisal methods are described in the text.

Limitations

  • The paper has no formal limitations section; it states that the exact azole resistance mechanism is not entirely clear, iron homeostasis mechanisms in *C. glabrata* remain unknown, it is unclear how *Candida* biofilm structure affects mucosal infection and host immunity, and acid stress tolerance has not been extensively investigated.
  • Evident from the text: as a narrative review, it lacks a systematic search strategy, quantitative synthesis, and formal risk-of-bias assessment.
  • Evident from the text: many cited findings derive from in vitro assays or murine models, which may limit direct clinical generalizability.

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

Integrity signals

Registry

Crossref · 10.3390/jof7080667

Cites

117 of 117 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 112 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Biofilms of C. glabrata and C. tropicalis do not possess persister cells.

    “In contrast, biofilms of C. glabrata and C. tropicalis do not possess such persister cells [13,43].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [13] Galocha, M., Pais, P., Cavalheiro, M., Pereira, D., Viana, R., and Teixeira, M.C. (2019). Divergent approaches to virulence in C. Albicans and C. Glabrata: Two sides of the same coin. Int. J. Mol. Sci., 20. source

      Not checked in the free run.

    • cites [43] Arendrup, 2017, Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment, J. Infect. Dis. source

      Not checked in the free run.

  • Premisecitation

    Most invasive candidiasis caused by C. glabrata is associated with biofilm growth.

    “Recent evidence indicates that most IC caused by C. glabrata is associated with biofilm growth [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Sardi, 2013, Candida species: Current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options, J. Med. Microbiol. source

      Not checked in the free run.

  • Premisecitation

    Fungal biofilms show higher antifungal resistance than planktonic populations.

    “Fungal biofilms show properties different from planktonic (free-living) populations, including a higher antifungal resistance level [39].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Pierce, 2008, A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing, Nat. Protoc. source

      Not checked in the free run.

  • Premisecitation

    The presence of persister cells in biofilms is mainly responsible for biofilm resistance.

    “Al-Dhaheri and Douglas [46] found that the presence of persister cells in biofilms is mainly responsible for biofilm resistance.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Douglas, 2008, Absence of Amphotericin B-Tolerant Persister Cells in Biofilms of Some Candida Species, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • Premisecitation

    C. glabrata cell wall is associated with serine protease Cwp1 (ORF: CBS138), a gelatinolytic enzyme.

    “C. glabrata is exceptional from this rule because the cell wall is associated with serine protease, Cwp1 (ORF: CBS138)—a gelatinolytic enzyme [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Bochenska, 2018, Extracellular proteinases of Candida species pathogenic yeasts, Mol. Oral Microbiol. source

      Not checked in the free run.

  • May combine two claims. 36
  • Classified as probably not a substantial claim. 27

  • May combine two claims.

    Premisenone given

    C. glabrata has well-characterised genes including ACE2 (CgACE2), a transcription factor that serves as a negative regulator of virulence.

    “Candida glabrata has well-characterised genes, including ACE2 (CgACE2), a transcription factor that serves as a negative regulator of virulence.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    C. glabrata accounts for approximately 15-25% of invasive clinical cases.

    “It accounts for approximately 15–25% of invasive clinical cases [8,11,12].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [8] Kounatidis, 2018, A Host-Pathogen Interaction Screen Identifies ada2 as a Mediator of Candida glabrata Defenses against Reactive Oxygen Species, G3 Genes Genomes Genet. source

      Not checked in the free run.

    • cites [11] McCarty, 2016, Invasive Candidiasis, Infect. Dis. Clin. N. Am. source

      Not checked in the free run.

    • cites [12] Pfaller, 2007, Epidemiology of Invasive Candidiasis: A Persistent Public Health Problem, Clin. Microbiol. Rev. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Candida glabrata is the second most isolated Candida species associated with invasive candidiasis behind C. albicans.

    “It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    EPA-family adhesins facilitate C. glabrata attachment to host epithelial cells and assist in macrophage entry.

    “These adhesins facilitate C. glabrata attachment to host epithelial cells and assist in macrophage entry [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] 2018, Deletion of ADA2 Increases Antifungal Drug Susceptibility and Virulence in Candida glabrata, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both the ace2 mutant and Evo strain have enhanced virulence.

    “Both mutants have enhanced virulence.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    C. glabrata lacks yeast-to-hyphae switching and grows only in the yeast form, contrary to C. albicans.

    “Candida glabrata lacks yeast-to-hyphae switching, it grows only in the yeast form, contrary to the virulent switch of C. albicans.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Invasive candidiasis due to C. glabrata causes substantial morbidity and mortality of approximately 40-60%, perhaps due to inherent low susceptibility to azoles.

    “Invasive candidiasis due to C. glabrata causes substantial morbidity and mortality of approximately 40–60%, perhaps due to the inherent low susceptibility of C. glabrata to the most commonly used azoles [3].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Timmermans, B., De Las Peñas, A., Castaño, I., and Van Dijck, P. (2018). Adhesins in Candida glabrata. J. Fungi, 4. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing). May combine two claims.

    Premisecitation

    The pathogenicity of C. glabrata appears to be independent of yeast morphology because the species is incapable of hyphae formation.

    “Galocha et al. [13] viewed that the pathogenicity of C. glabrata appears to be independent of the morphology of the yeast as this species is incapable of hyphae formation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Galocha, M., Pais, P., Cavalheiro, M., Pereira, D., Viana, R., and Teixeira, M.C. (2019). Divergent approaches to virulence in C. Albicans and C. Glabrata: Two sides of the same coin. Int. J. Mol. Sci., 20. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The evolved (Evo) strain is a hyper-virulent C. glabrata strain with a single nucleotide mutation in the chitin synthase gene CHS2.

    “The evolved (Evo) strain is another hyper-virulent C. glabrata strain with a single nucleotide mutation in the chitin synthase gene CHS2.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    C. glabrata requires iron as an essential micronutrient for its growth during infection.

    “Candida glabrata requires iron as an essential micronutrient for its growth during infection.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    C. glabrata developed acquired resistance to antifungal drugs through prolonged exposure.

    “Arendrup and Patterson [43] argued that C. glabrata developed acquired resistance to antifungal drugs through prolonged exposure.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Arendrup, 2017, Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment, J. Infect. Dis. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims.

    Premisecitation

    Overexpression of transcription factor CgCrz1p enhances viability, cellular biomass, and pyruvate yields at low pH.

    “Contrary to the view of Yan et al. [66] that overexpression of the transcription factor CgCrz1p enhances viability, cellular biomass, and pyruvate yields at a low pH.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Yan, 2016, Crz1p Regulates pH Homeostasis in Candida glabrata by Altering Membrane Lipid Composition, Appl. Environ. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ICL1 is necessary for acetate, ethanol, and oleic acid utilisation and partly required for lactate utilisation in C. glabrata.

    “Moreover, the findings reported the necessity of isocitrate lyase (ICL1), the glyoxylate cycle gene for acetate utilisation, ethanol, and oleic acid, and partly required for the utilisation of lactate in C. glabrata.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    C. glabrata lacks hyphal formation and phagosomal extrusions to escape phagocytic cell attack, contrary to C. albicans.

    “Candida glabrata lacks hyphal formation and phagosomal extrusions to escape the phagocytic cells attack contrary to C. albicans [68,69].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [68] Yih, C.S., Than, L., and Lung, T. (2012). Candida glabrata: Niche adaptation and mechanisms of survival. Updates in Medical Microbiology, Universiti Putra Malaysia Press.

      Not checked in the free run.

    • cites [69] Roetzer, 2010, Autophagy supports Candida glabrata survival during phagocytosis, Cell. Microbiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Approximately more than 140 alterations in the ERG11 target gene have been described.

    “Approximately more than 140 alterations in the ERG11 target gene have been described.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    Both C. krusei and some C. glabrata have intrinsic resistance to fluconazole.

    “It is a well-known fact that both C. krusei and some C. glabrata have intrinsic resistance to fluconazole.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Lactate-grown C. glabrata cells resist killing by macrophages and have developed distinct tactics for intracellular survival and escaping phagocytosis.

    “Lactate-grown C. glabrata cells, for example, resist killing by macrophages and have developed distinct tactics for intracellular survival killing and escaping phagocytosis [41].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Mota, 2015, Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate, Front. Microbiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    Aneuploidy causes a transcriptional response that results in gene expression in chromosomes.

    “Torres et al. [91] viewed that aneuploidy causes a transcriptional response that results in gene expression in chromosomes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [91] Torres, 2007, Effects of Aneuploidy on Cellular Physiology and Cell Division in Haploid Yeast, Science source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Aged cells exhibit different lipid composition that leads to the emergence of azole resistance.

    “Aged cells exhibit different lipid composition that leads to the emergence of azole resistance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    C. glabrata grows optimally at 37 °C and can grow at 42 °C under heat-stressed conditions.

    “Candida glabrata grows optimally at 37 °C and, therefore, thrives best in the human host and can grow at 42 °C under heat-stressed conditions [18,57].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] 2016, The birth of a deadly yeast: Tracing the evolutionary emergence of virulence traits in Candida gla-brata, FEMS Yeast Res.

      Not checked in the free run.

    • cites [57] Roetzer, 2008, Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors, Mol. Microbiol. source

      Not checked in the free run.

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

    Premisecitation

    Prolonged administration of antifungal drugs for treatment and prevention is the primary cause of the emergence of resistant strains.

    “Moreover, Jensen et al. [82] supported the view that prolonged administration of antifungal drugs for treatment and prevention is the primary cause of the emergence of resistant strains.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [82] Jensen, 2016, Posttreatment Antifungal Resistance among Colonizing Candida Isolates in Candidemia Patients: Results from a Systematic Multicenter Study, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BPY40 was azole sensitive, while BPY41 was azole-resistant.

    “The former was azole sensitive, while the latter was azole-resistant.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Ferrari, 2011, Loss of mitochondrial functions associated with azole resistance in Candida glabrata results in enhanced virulence in mice, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. glabrata possesses numerous resistance mechanisms to fluconazole, including fluctuation of gene regulation, genetic mutations, and cross-resistance among azole derivatives.

    “Candida glabrata possesses numerous resistance mechanisms to fluconazole, including fluctuation of gene regulation, genetic mutations, and cross-resistance among azole derivatives [86].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] Gohar, 2017, Expression patterns of ABC transporter genes in fluconazole-resistant Candida glabrata, Mycopathologia source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. glabrata does not germinate into hyphae yet is virulent.

    “Considering the role of dimorphism as a factor for pathogenicity in some Candida species, C. glabrata is exceptional; it does not germinate into hyphae yet is virulent [73].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] Benito, 2017, Yeast community in traditional Portuguese Serpa cheese by culture-dependent and -independent DNA approaches, Int. J. Food Microbiol. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Neutrophils in the host selectively kill younger cells, leaving old yeast cells to accumulate.

    “The in vivo study by Bhattacharya et al. [76] viewed that the neutrophils cells in the host selectively kill younger cells, leaving the old yeast cells to accumulate.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] Bhattacharya, 2018, Enhanced Efflux Pump Activity in Old Candida glabrata Cells, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mutations in ERG11 and PDR1 can mediate azole resistance; daughter cells inherit the mutations and persist.

    “Mutations in ERG11 and PDR1 can mediate azole resistance; daughter cells will inherit the mutations and persist [76].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Bhattacharya, 2018, Enhanced Efflux Pump Activity in Old Candida glabrata Cells, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    C. glabrata shows a unique immune system evasion mechanism and survives after cellular engulfment despite antifungal presence.

    “Thus, C. glabrata shows a unique immune system evasion mechanism and survives after cellular engulfment despite the antifungal presence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The high-affinity reductive iron uptake system is necessary for metabolism in the presence of alternate carbon sources and for growth under in vitro and in vivo iron-limiting conditions.

    “According to the findings of Srivastava et al. [50] that the high-affinity reductive iron uptake system is necessary for metabolism in the presence of alternate carbon sources and for growth under both in vitro and in vivo iron-limiting conditions.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Srivastava, 2014, A systematic analysis reveals an essential role for high-affinity iron uptake system, haemolysin and CFEM domain-containing protein in iron homoeostasis and virulence in Candida glabrata, Biochem. J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The free nitrogen atom of the azole ring binds an iron atom within the enzyme haem group, preventing oxygen activation and causing demethylation of lanosterol that inhibits ergosterol biosynthesis.

    “More specifically, the free nitrogen atom of the azole ring binds an iron atom within the enzyme haem group. Thus, it prevents oxygen activation and causes demethylation of lanosterol that inhibits the ergosterol biosynthesis process.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Duplications increase the level of drug resistance because ABC transporters are implicated in pleiotropic drug resistance.

    “Duplications increase the level of drug resistance, as ABC transporters are implicated in pleiotropic drug resistance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Sasso et al. reported increasing isolation of echinocandin-resistant C. glabrata strains, significantly associated with FKS1 and FKS2 gene mutations.

    “However, Sasso et al. [103] reported increasing isolation of echinocandin C. glabrata-resistant strains, significantly associated with FKS1 and FKS2 gene mutations.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [103] Sasso, 2017, Rapid emergence of FKS mutations in Candida glabrata isolates in a peritoneal candidiasis, Med. Mycol. Case Rep. source

      Not checked in the free run.

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

    Premisecitation

    Amphotericin B is used in the pharmacotherapy of life-threatening fungal infections.

    “It is used in the pharmacotherapy of life-threatening fungal infections [107].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [107] Rodrigues, 2016, Candida glabrata’s recurrent infections: Biofilm formation during Amphotericin B treatment, Lett. Appl. Microbiol. source

      Not checked in the free run.

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

    Premisecitation

    Echinocandins are recommended as first-line therapy for non-neutropenic patients with suspected severe IC associated with C. albicans and C. glabrata.

    “Echinocandins are recommended as first-line therapy for non-neutropenic patients associated with C. albicans and C. glabrata in suspected severe IC conditions [100].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [100] Wanjare, 2016, Caspofungin MIC Distribution amongst Commonly Isolated Candida Species in a Tertiary Care Centre—An Indian Experience, J. Clin. Diagn. Res.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    All isolates were highly susceptible to anidulafungin except C. glabrata with 10% resistance.

    “All isolates were highly susceptible to anidulafungin except C. glabrata with 10% resistance.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] Aslani, 2018, Identification of uncommon oral yeasts from cancer patients by MALDI-TOF mass spectrometry, BMC Infect. Dis. source

      Not checked in the free run.

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

    Premisecitation

    Amphotericin B is a fungicidal polyene and has shown promising activity against many Candida species.

    “Amphotericin B (AmB) is a fungicidal polyene and has shown promising activity against many Candida species.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [107] Rodrigues, 2016, Candida glabrata’s recurrent infections: Biofilm formation during Amphotericin B treatment, Lett. Appl. Microbiol. source

      Not checked in the free run.

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

    Premisecitation

    Echinocandins exist according to international guidelines in three available types: caspofungin, anidulafungin, and micafungin.

    “Echinocandins exist according to the international guidelines in three available types (caspofungin, anidulafungin, and micafungin).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] Yeoh, 2018, Echinocandins for management of invasive candidiasis in patients with liver disease and liver transplantation, Infect. Drug Resist. source

      Not checked in the free run.

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

    Premisecitation

    The findings attributed lower resistance of C. glabrata with biofilms against amphotericin and not about the low biofilm content of the isolates tested.

    “The findings attributed lower resistance of C. glabrata with biofilms against amphotericin and not about the low biofilm content of the isolates tested.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [110] Tay, 2014, Occurrence and Characterization of Candida nivariensis from a Culture Collection of Candida glabrata Clinical Isolates in Malaysia, Mycopathologia source

      Not checked in the free run.

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

    Premisecitation

    Echinocandins differ based on route of metabolism, half-life, and safety.

    “They differ based on the route of metabolism, half-life, and safety [102].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] Yeoh, 2018, Echinocandins for management of invasive candidiasis in patients with liver disease and liver transplantation, Infect. Drug Resist. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both human and fungal cell biomembranes are primary targets of amphotericin B, impairing physiological processes in membranes, particularly adenocarcinoma cells.

    “This is because both human and fungal cells’ biomembranes are the primary targets of the AmB. Thus, impairing the physiological processes that take place in the membranes, particularly adenocarcinoma cells [108].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Grela, 2018, Imaging of human cells exposed to an antifungal antibiotic amphotericin B reveals the mechanisms associated with the drug toxicity and cell defence, Sci. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The prevalence of echinocandin resistance among Candida strains remains low, with around 4% observed in C. glabrata and less than 1% in C. albicans.

    “The prevalence of echinocandin resistance among Candida strains remains low, with around 4% observed in C. glabrata and less than 1% in C. albicans [103].”
    • Also stated in: § 3.1. Types of Drug Resistance Mechanisms · plain
      “Shields et al. [105] reported low echinocandin resistance, around 4% for C. glabrata and less than 1% for C. albicans.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [103] Sasso, 2017, Rapid emergence of FKS mutations in Candida glabrata isolates in a peritoneal candidiasis, Med. Mycol. Case Rep. source

      Not checked in the free run.

    • cites [105] Shields, 2016, Rate of FKS Mutations among Consecutive Candida Isolates Causing Bloodstream Infection, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intrinsic resistance to echinocandins is rare and primarily only observed in Candida parapsilosis.

    “Intrinsic resistance to echinocandins is rare and primarily only observed in Candida parapsilosis [103].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [103] Sasso, 2017, Rapid emergence of FKS mutations in Candida glabrata isolates in a peritoneal candidiasis, Med. Mycol. Case Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Echinocandins were launched in the early 2000s and became first-line treatment following the emergence of C. glabrata with reduced susceptibility to fluconazole.

    “Echinocandins were launched in the early 2000s and became the first-line treatment following the emergence of C. glabrata with reduced susceptibility to fluconazole Colombo et al. [101].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [101] Colombo, 2017, Emerging multidrug-resistant Candida species, Curr. Opin. Infect. Dis. source

      Not checked in the free run.

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

    Premisecitation

    According to CLSI M27-A2, fluconazole interpretative breakpoints for in vitro testing of Candida species using broth microdilution are ≤8 μg mL−1 for susceptible, 16-32 μg ml−1 for susceptible-dose dependent, and ≥64 μg mL−1 for resistant.

    “According to the clinical laboratory standard institute (CLSI) M27-A2, the interpretative breakpoints for fluconazole for in vitro testing of Candida species using broth microdilution method is ≤8 µg mL−1 for susceptible (S), 16–32 µg ml−1 for susceptible-dose dependent (S-DD), and ≥64 µg mL−1 for resistant (R) [99].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [99] Wayne, P. (2017). Clinical and laboratory standards institute: Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved Standard, Clinical and Laboratory Standards Institute.

      Not checked in the free run.

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

    Premisecitation

    Newer azoles such as posaconazole and voriconazole replaced fluconazole in prophylaxis routines and have raised similar concerns about resistance and drug-drug interactions as observed in azoles.

    “These findings agreed with the view of Larkin et al. [98] that newer azoles, such as posaconazole and voriconazole, replaced fluconazole in prophylaxis routines and have raised similar concerns about resistance and drug-drug interactions as observed in azoles.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Larkin, 2018, Biofilms and beyond: Expanding echinocandin utility, J. Antimicrob. Chemother. source

      Not checked in the free run.

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

    Premisecitation

    One major setback of echinocandins oral administration is inadequate bioavailability, so it is often given intravenously.

    “One major setback of echinocandins oral administration is the inadequate bioavailability, and therefore, it is often given intravenously [104].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [104] Walker, 2009, Methods in Molecular Biology. TM Series Editor, Life Sci.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Aslani et al. reported that 39% of yeast strains from cancer patients showed higher MIC values to amphotericin B, with MIC90 values of 4 μg/mL.

    “The study of Aslani et al. [111] reported that 39% of yeast strains from cancer patients showed higher MIC values to AmB, with MIC90 values of 4 μg/mL.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [111] Shokohi, 2018, Candida infanticola and Candida spencermartinsiae yeasts: Possible emerging species in cancer patients, Microb. Pathog. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Candida species possess many virulence factors, including secretion of hydrolytic enzymes, host cell wall adherence, and biofilm formation.

    “Moreover, Candida species possess many virulence factors, including secretion of hydrolytic enzymes host cell wall adherence, and biofilm formation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    C. glabrata cells become engulfed in macrophages and quickly adopt other mechanisms of survival by undergoing massive division and release upon rupture.

    “Candida glabrata cells become engulfed in the macrophages. They quickly adopt other mechanisms of survival by undergoing massive division and release upon rupture.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Candida cells have the capacity to rapidly adjust to external aggressions, suggesting why patients undergoing amphotericin B therapy may still manifest resilient Candida infections.

    “This underlines the capacity of Candida cells to rapidly adjust to external aggressions. Thus, this suggests why patients undergoing AmB therapy may still manifest resilient Candida infections.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [107] Rodrigues, 2016, Candida glabrata’s recurrent infections: Biofilm formation during Amphotericin B treatment, Lett. Appl. Microbiol. source

      Not checked in the free run.

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

    Interpretationnone given

    Alteration of host interaction factors facilitates opportunistic harmless commensal Candida species to become potentially life-threatening human pathogens.

    “The alteration of host interaction factors facilitates opportunistic harmless commensal Candida species to become potentially life-threatening human pathogens.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    Rodrigues et al. viewed that C. glabrata can produce biofilms in the presence of amphotericin B therapeutic concentrations due to high concentrations of carbohydrate and β-1,3 glucan on biofilm matrices.

    “In contrast, Rodrigues et al. [107] viewed that C. glabrata can produce biofilms in the presence of AmB therapeutic concentrations due to the high concentrations of carbohydrate and β-1,3 glucan on the biofilm matrices.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [107] Rodrigues, 2016, Candida glabrata’s recurrent infections: Biofilm formation during Amphotericin B treatment, Lett. Appl. Microbiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Acquired and intrinsic resistance to fluconazole and rapid resistance development to a few available antifungal drugs are of significant clinical concern.

    “Moreover, acquired and intrinsic resistance to fluconazole and rapid resistance development to a few available antifungal drugs are of significant clinical concern.”
    Quote in the paperNot a substantial claim
52 of 52

  • The authors state this as an assumption.

    The mechanisms of biofilm resistance include elevated cellular density, exopolymeric protective effect, differential upregulation of resistance genes and efflux pumps, and a subpopulation within the biofilm community.

    “The resistance development due to biofilm is complex and multifactorial; among the assumed mechanisms are (i) the elevated cellular density within the biofilm, (ii) the exopolymeric protective effect of the biofilm, (iii) differential upregulation of genes linked to resistance and those encoding efflux pumps, and (iv) the presence of a subpopulation within the biofilm community.”

  • The paper relies on this without support.

    The four databases Google Scholar, ScienceDirect, PubMed, and Scopus cover the relevant published research on C. glabrata pathogenicity.

    “The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus.”
2 of 2

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?

Cites

Flagged first, then by citations

3 of the 120 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Molina, 2000, Protein Localisation Approaches for Understanding Yeast Cell Wall Biogenesis, Histol. Stud. Yeast, 612, 601
  2. Walker, 2009, Methods in Molecular Biology. TM Series Editor, Life Sci., 531, 588

Cited by

Sorted by citations

Related

Authors
Hassan, Y., Chew, S. Y., & Than, L. T. L.
Affiliations
Universiti Putra Malaysia (MY)
Corresponding author
Than, Leslie Thian Lung
ORCID
Venue
Journal of Fungi
Publisher
MDPI AG
Published
2021-08-17
Volume
7
Issue
8
Pages
667
ISSN
2309-608X (ISSN-L)
DOI
10.3390/jof7080667
PMC
PMC8398317
OpenAlex
W3194477778
Semantic Scholar
11389a27e141b112f6c043a2bb401fd6354cb150
Cited by
170
References
120
Citations by year
2026: 35 · 2025: 41 · 2024: 42 · 2023: 26 · 2022: 20 · 2021: 6
FWCI
2.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Fungi (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Universiti Putra Malaysia Institutional Repository (Universiti Putra Malaysia) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Greater South Information System
Funders
Universiti Putra Malaysia (GP-IPS/2018/9612400)
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 › Yeasts and Rust Fungi Studies
Keywords
Candida glabrata, invasive candidiasis, virulence factors, antifungal resistance, fluconazole resistance, azole resistance, biofilm formation, host defense evasion, iron regulation, hydrolytic enzymes, phospholipase, proteolytic enzymes, hemolysin, critically ill patients

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.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review