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Cited by 128Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Candida glabrata: A Lot More Than Meets the Eye

Open access
Kumar, Kundan, Askari, Fizza, Sahu, Mahima Sagar, Kaur, Rupinder·2019·Microorganisms
DOI 10.3390/microorganisms7020039PMC PMC6407134
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Abstract

Candida glabrata is an opportunistic human fungal pathogen that causes superficial mucosal and life-threatening bloodstream infections in individuals with a compromised immune system. Evolutionarily, it is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to the most prevalent Candida bloodstream pathogen, C. albicans. C. glabrata is a haploid budding yeast that predominantly reproduces clonally. In this review, we summarize interactions of C. glabrata with the host immune, epithelial and endothelial cells, and the ingenious strategies it deploys to acquire iron and phosphate from the external environment. We outline various attributes including cell surface-associated adhesins and aspartyl proteases, biofilm formation and stress response mechanisms, that contribute to the virulence of C. glabrata. We further discuss how, C. glabrata, despite lacking morphological switching and secreted proteolytic activity, is able to disarm macrophage, dampen the host inflammatory immune response and replicate intracellularly.

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Written from the paper’s full text.

TL;DR

Candida glabrata is an opportunistic human fungal pathogen that is evolutionarily closer to Saccharomyces cerevisiae than to Candida albicans and causes up to 29% of Candida bloodstream infections. This review synthesizes its genomic architecture, virulence traits, nutrient acquisition and stress signaling pathways, and interactions with host epithelial, endothelial and immune cells.

Key findings

  • Epidemiology and genome: C. glabrata accounts for up to 29% of total Candida bloodstream infections; it is second most common after C. albicans in Northern Europe/USA but third or fourth in Asia. Its haploid genome is 12.3 Mb across 13 chromosomes with 5293 ORFs, of which only 238 (4.5%) are experimentally verified; it shows 88% synteny with S. cerevisiae and has 337 genes absent in S. cerevisiae.
  • Virulence factors: The genome encodes 67 putative adhesins, including 17–23 Epa subfamily I proteins depending on isolate (CBS138: 17; BG2: 23), and 11 GPI-anchored aspartyl proteases (CgYps1–11) despite lacking secreted proteolytic activity. Biofilms are matrix-embedded yeast structures with proteins/carbohydrates including β-1,3 glucan; CgYps1 is required for acid stress survival, and the Cgyps1-11Δ mutant has cell wall and vacuole defects.
  • Nutrient acquisition and stress: Iron acquisition includes siderophore-mediated uptake via CgSit1 and reductive iron acquisition, but not receptor-mediated haem uptake; the iron regulon comprises 51 genes. Phosphate starvation acts through CgPho4 and the CgPmu1–3 phosphatases, while stress responses involve CgMsn2/4, CgCta1, CgSod1/2, PKC–CgSlt2, calcineurin, HOG–CgHog1 and CgIre1.
  • Host interaction: C. glabrata survives and replicates in macrophages, fails to trigger substantial MAPK/NF-κB activation, and induces GM-CSF but not TNF-α, IL-6, IL-8, IL-12 or IFN-γ; Syk/NLRP3-dependent IL-1β is produced, and CgYapsins suppress this response. Epa1, Epa6 and Epa7 are recognized by NKp46/NCR1, and C. glabrata lacks yeast-to-hypha switching and is less pathogenic than C. albicans.

Methods

  • Design: narrative review; no primary experiments or new data are reported.
  • Data/sample: published literature on C. glabrata genomics, virulence, nutrient acquisition, stress signaling and host-cell interactions; no systematic search or meta-analysis is described.
  • Main analysis: thematic synthesis of cited studies, including comparisons with S. cerevisiae and C. albicans.

Limitations

  • Stated: the authors note that “because of space limitations” antifungal tolerance/resistance factors are not discussed and refer readers to other reviews; they also identify multiple areas as yet to be characterized (e.g., C. glabrata–endothelial and –neutrophil interactions, roles of some iron transporters, direct links between yapsin activity and cellular processes).
  • Evident from the text: as a narrative review, it lacks systematic search/inclusion criteria and quantitative synthesis, so coverage and conclusions depend on selected cited literature.

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

Integrity signals

Registry

Crossref · 10.3390/microorganisms7020039

Cites

153 of 153 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

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  • Premisecitation

    Molecular phylogenetic and genome analysis have revealed that the three human pathogenic species of the glabrata group, C. glabrata, C. nivariensis and C. bracarenses, are polyphyletic in origin.

    “Intriguingly, molecular phylogenetic and genome analysis have revealed three human pathogenic species, C. glabrata, C. nivariensis and C. bracarenses of the glabrata group, to be polyphyletic in origin [18,25].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

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    • cites [25] Ksiezopolska, 2018, Patterns of genomic variation in the opportunistic pathogen Candida glabrata suggest the existence of mating and a secondary association with humans, Curr. Biol. source

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  • Premisecitation

    The opportunistic pathogenic lifestyle of C. glabrata is thought to have arisen independently from that of C. albicans.

    “The reproduction mode in C. glabrata is predominantly clonal, and the opportunistic pathogenic lifestyle of C. glabrata is also thought to have arisen independently from that of C. albicans [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Ksiezopolska, 2018, Patterns of genomic variation in the opportunistic pathogen Candida glabrata suggest the existence of mating and a secondary association with humans, Curr. Biol. source

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    The capability to infect humans appears to have emerged independently within the Nakaseomyces.

    “As the capability to infect humans appears to have emerged independently within the Nakaseomyces [18], C. glabrata may have acquired a unique set of pathogenesis attributes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

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  • Premisecitation

    Evolutionarily, C. glabrata is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to C. albicans.

    “Evolutionarily, it is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to the most prevalent Candida bloodstream pathogen, C. albicans.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] Dujon, 2004, Genome evolution in yeasts, Nature source

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    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

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  • Premisecitation

    The C. glabrata genome consistently exhibits lower global redundancy.

    “The C. glabrata genome consistently exhibits lower global redundancy [17].”
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    • cites [17] Dujon, 2004, Genome evolution in yeasts, Nature source

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    Premisecitation

    C. glabrata is an opportunistic human fungal pathogen that causes superficial mucosal and life-threatening bloodstream infections in individuals with a compromised immune system.

    “Candida glabrata is an opportunistic human fungal pathogen that causes superficial mucosal and life-threatening bloodstream infections in individuals with a compromised immune system.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] Pfaller, 2011, Candida bloodstream infections: Comparison of species distribution and resistance to echinocandin and azole antifungal agents in Intensive Care Unit (ICU) and non-ICU settings in the SENTRY antimicrobial surveillance program (2008–2009), Int. J. Antimicrob. Agents source

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    • cites [2] Montagna, 2014, Candidemia in intensive care unit: A nationwide prospective observational survey (GISIA-3 study) and review of the European literature from 2000 through 2013, Eur. Rev. Med. Pharmacol. Sci.

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    Premisecitation

    C. glabrata accounts for up to 29% of total Candida bloodstream infections.

    “Candida glabrata is an opportunistic human fungal pathogen that accounts for up to 29% of total Candida bloodstream infections [1,2].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Pfaller, 2011, Candida bloodstream infections: Comparison of species distribution and resistance to echinocandin and azole antifungal agents in Intensive Care Unit (ICU) and non-ICU settings in the SENTRY antimicrobial surveillance program (2008–2009), Int. J. Antimicrob. Agents source

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    • cites [2] Montagna, 2014, Candidemia in intensive care unit: A nationwide prospective observational survey (GISIA-3 study) and review of the European literature from 2000 through 2013, Eur. Rev. Med. Pharmacol. Sci.

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    The annotated C. glabrata genome contains 13 chromosomes, named A to M, and is 12.3 Mb in size.

    “The annotated genome contains 13 chromosomes, named as Chromosome A to M, and is of 12.3 Mb in size [17].”
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    • cites [17] Dujon, 2004, Genome evolution in yeasts, Nature source

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    C. glabrata belongs to the non-CTG Saccharomycetaceae clade in which the CTG codon encodes leucine.

    “C. glabrata is a haploid budding yeast, and belongs to the non-CTG, Saccharomycetaceae clade in which the CTG codon encodes leucine [17,18].”
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    • cites [17] Dujon, 2004, Genome evolution in yeasts, Nature source

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    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

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    Premisecitation

    C. glabrata is a haploid budding yeast that predominantly reproduces clonally.

    “C. glabrata is a haploid budding yeast that predominantly reproduces clonally.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [17] Dujon, 2004, Genome evolution in yeasts, Nature source

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    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

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    • cites [25] Ksiezopolska, 2018, Patterns of genomic variation in the opportunistic pathogen Candida glabrata suggest the existence of mating and a secondary association with humans, Curr. Biol. source

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    Premisecitation

    The C. glabrata genome shows plasticity, and alterations in karyotype and chromosome size have been observed in clinical isolates and the reference strain CBS138.

    “The C. glabrata genome shows plasticity, and alterations in karyotype and chromosome size have been observed in clinical isolates and the reference strain CBS138 [19,20,21].”
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    • cites [19] Jong, 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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    • cites [20] Bader, 2012, Gross karyotypic and phenotypic alterations among different progenies of the Candida glabrata CBS138/ATCC2001 reference strain, PLoS ONE source

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    • cites [21] Ahmad, 2013, Small chromosomes among Danish Candida glabrata isolates originated through different mechanisms, Antonie van Leeuwenhoek Int. J. Gen. Mol. Microbiol. source

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    C. glabrata prevalence varies with geographic area.

    “Its prevalence varies with the geographic area [2,3,4].”
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    • cites [2] Montagna, 2014, Candidemia in intensive care unit: A nationwide prospective observational survey (GISIA-3 study) and review of the European literature from 2000 through 2013, Eur. Rev. Med. Pharmacol. Sci.

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    • cites [3] Yapar, 2014, Epidemiology and risk factors for invasive candidiasis, Ther. Clin. Risk Manag. source

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    • cites [4] Chakrabarti, 2014, Incidence, characteristics and outcome of ICU-acquired candidemia in India, Intensive Care Med. source

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    Premisecitation

    In Asia, C. glabrata ranks as the third or fourth most prevalent invasive Candida pathogen.

    “While C. glabrata is the second most common bloodstream Candida species after C. albicans in Northern Europe and the USA [1,5,6], it ranks as the third or fourth most prevalent invasive Candida pathogen in Asia [4,6,7].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [4] Chakrabarti, 2014, Incidence, characteristics and outcome of ICU-acquired candidemia in India, Intensive Care Med. source

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    • cites [6] Guinea, 2014, Global trends in the distribution of Candida species causing candidemia, Clin. Microbiol. Infect. source

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    • cites [7] Tan, 2015, Incidence and species distribution of candidaemia in Asia: A laboratory-based surveillance study, Clin. Microbiol. Infect. source

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    Premisecitation

    Both C. glabrata and S. cerevisiae belong to the Whole Genome Duplication (WGD) group.

    “Both C. glabrata and S. cerevisiae belong to the Whole Genome Duplication (WGD) group, and are assumed to have arisen from the same tetraploid hybrid ancestor, which existed about 100-200 million years ago [18].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

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    • The authors state this as an assumption: C. glabrata and S. cerevisiae arose from the same tetraploid hybrid ancestor about 100-200 million years ago.

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

    Premisecitation

    Recent epidemiological surveys show a decrease in the frequency of C. albicans and an increased prevalence of non-albicans Candida.

    “Recent epidemiological surveys have shown a decrease in the frequency of C. albicans and an increased prevalence of non-albicans Candida [3,5,6].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Yapar, 2014, Epidemiology and risk factors for invasive candidiasis, Ther. Clin. Risk Manag. source

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    • cites [5] Diekema, 2012, The changing epidemiology of healthcare-associated candidemia over three decades, Diagn. Microbiol. Infect. Dis. source

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    • cites [6] Guinea, 2014, Global trends in the distribution of Candida species causing candidemia, Clin. Microbiol. Infect. source

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    Premisecitation

    C. glabrata is a causative agent of urinary tract and vaginal infections.

    “C. glabrata is also a causative agent of urinary tract and vaginal infections [10,11].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] 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 [11] Achkar, 2010, Candida infections of the genitourinary tract, Clin. Microbiol. Rev. source

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    Premisecitation

    Within the Saccharomycetaceae family, C. glabrata belongs to the genus Nakaseomyces, which contains three pathogenic species and three environmental species.

    “As mentioned earlier, within the Saccharomycetaceae family, C. glabrata belongs to the genus Nakaseomyces, which contains three pathogenic species (C. glabrata, C. nivariensis and C. bracarenses) and three environmental species (C. castellii, Kluyveromyces delphensis and K. bacillisporus) [18].”
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    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

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    Premisecitation

    In Northern Europe and the USA, C. glabrata is the second most common bloodstream Candida species after C. albicans.

    “While C. glabrata is the second most common bloodstream Candida species after C. albicans in Northern Europe and the USA [1,5,6], it ranks as the third or fourth most prevalent invasive Candida pathogen in Asia [4,6,7].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Pfaller, 2011, Candida bloodstream infections: Comparison of species distribution and resistance to echinocandin and azole antifungal agents in Intensive Care Unit (ICU) and non-ICU settings in the SENTRY antimicrobial surveillance program (2008–2009), Int. J. Antimicrob. Agents source

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    • cites [5] Diekema, 2012, The changing epidemiology of healthcare-associated candidemia over three decades, Diagn. Microbiol. Infect. Dis. source

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    • cites [6] Guinea, 2014, Global trends in the distribution of Candida species causing candidemia, Clin. Microbiol. Infect. source

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    Premisecitation

    C. albicans belongs to the CTG clade wherein the CTG codon is translated as serine instead of leucine.

    “Contrarily, C. albicans belongs to the CTG clade wherein the CTG codon is translated as serine instead of leucine [17,18].”
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    • cites [17] Dujon, 2004, Genome evolution in yeasts, Nature source

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    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

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    Premisecitation

    Of a total of 5293 open reading frames in the C. glabrata genome, only 238 (4.5%) are verified with experimental evidence for the existence of their gene products.

    “Of a total of 5293 open reading frames (ORFs) in the C. glabrata genome, only 238 (4.5%) ORFs are verified with some experimental evidence for the existence of their gene products [www.candidagenome.org].”
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    • cites [www.candidagenome.org]

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    C. glabrata bloodstream infections are commonly found in elderly individuals, diabetic patients and solid organ transplant recipients.

    “C. glabrata bloodstream infections are commonly found in elderly individuals, diabetic patients and solid organ transplant recipients [6,8,9].”
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    • cites [6] Guinea, 2014, Global trends in the distribution of Candida species causing candidemia, Clin. Microbiol. Infect. source

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    • cites [8] Pfaller, M.A., Andes, D.R., Diekema, D.J., Horn, D.L., Reboli, A.C., Rotstein, C., Franks, B., and Azie, N.E. (2014). Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: Data from the Prospective Antifungal Therapy (PATH) registry 2004–2008. PLoS ONE, 9. source

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    • cites [9] Khatib, 2016, Current trends in candidemia and species distribution among adults: Candida glabrata surpasses C. albicans in diabetic patients and abdominal sources, Mycoses source

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    Premisecitation

    Epa1 is a calcium-dependent lectin that aids adhesion to epithelial cells and macrophages.

    “The founding member of the Epa adhesin family, Epa1, is a calcium-dependent lectin, and aids adhesion to epithelial cells [32] and macrophages [33].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [32] Cormack, 1999, An adhesin of the yeast pathogen Candida glabrata mediating adherence to human epithelial cells, Science source

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    • cites [33] Kuhn, 2012, The Candida glabrata adhesin Epa1p causes adhesion, phagocytosis, and cytokine secretion by innate immune cells, FEMS Yeast Res. source

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    Premisecitation

    C. glabrata clinical isolates have varied numbers of adhesin-encoding genes and a distinct profile of cell wall proteins expressed at the cell surface.

    “Moreover, C. glabrata clinical isolates are known to have varied number of adhesin-encoding genes, and a distinct profile of cell wall proteins expressed at the cell surface [41,48,49].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [41] Dekker, 2015, Proteomic analysis of hyperadhesive Candida glabrata clinical isolates reveals a core wall proteome and differential incorporation of adhesins, FEMS Yeast Res. source

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    • cites [48] Beaudoing, 2017, Comparative genomics of two sequential Candida glabrata clinical isolates, G3 source

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    • cites [49] Salazar, 2017, Comparative genomic and transcriptomic analyses unveil novel features of azole resistance and adaptation to the human host in Candida glabrata, FEMS Yeast Res.

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    Premisecitation

    Adherence analysis of S. cerevisiae strains expressing ligand-binding domains of 15 Epa adhesins individually revealed significant, moderate and very weak adherence to human epithelial colorectal adenocarcinoma cells (Caco2) for Epa1, 6 and 7; Epa8, 9, 12, 15 and 23; and Epa2, 3, 11, 13, 19, 20 and 21, respectively.

    “Furthermore, adherence analysis of S. cerevisiae strains expressing ligand-binding domains of 15 Epa adhesins individually revealed significant, moderate and very weak adherence to human epithelial colorectal adenocarcinoma cells (Caco2) for Epa1, 6 and 7, Epa8, 9, 12, 15 and 23, and Epa2, 3, 11, 13, 19, 20 and 21, respectively [45].”
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    • cites [45] Diderrich, 2015, Structural hot spots determine functional diversity of the Candida glabrata epithelial adhesin family, J. Biol. Chem. source

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    Premisecitation

    Epa1, Epa6 and Epa7 show glycan ligand specificity, with Epa6 having the widest substrate specificity.

    “Despite the preference for the terminal galactose, Epa1, 6 and 7 showed glycan ligand specificity, with Epa6 having the widest substrate specificity [35,43].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [35] Zupancic, 2008, Glycan microarray analysis of Candida glabrata adhesin ligand specificity, Mol. Microbiol. source

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    • cites [43] Diderrich, 2012, Structural basis for promiscuity and specificity during Candida glabrata invasion of host epithelia, Proc. Natl. Acad. Sci. USA source

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    Premisecitation

    The sequenced fecal isolate CBS 138 contains 17 Epa-encoding genes, while the vaginal isolate BG2 contains 23 Epa-encoding genes.

    “The sequenced fecal isolate CBS 138 contains 17 Epa-encoding genes, while the widely used vaginal isolate BG2 contains 23 Epa-encoding genes [27,28].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27] Kraneveld, 2008, The cell wall of the human pathogen Candida glabrata: Differential incorporation of novel adhesin-like wall proteins, Eukaryot. Cell source

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    • cites [28] Kaur, 2005, A yeast by any other name: Candida glabrata and its interaction with the host, Curr. Opin. Microbiol. source

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    Premisecitation

    Secreted aspartyl proteases are key fungal virulence factors.

    “Secreted aspartyl proteases are key fungal virulence factors [28].”
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    • cites [28] Kaur, 2005, A yeast by any other name: Candida glabrata and its interaction with the host, Curr. Opin. Microbiol. source

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    Premisecitation

    The majority of Epa adhesins are encoded by sub-telomeric localized genes and regulated by epigenetic SIR-dependent transcriptional silencing.

    “The majority of Epa adhesins are encoded by sub-telomeric localized genes and regulated by epigenetic SIR (Silent Information Regulator)-dependent transcriptional silencing [27,29,30,31].”
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    • cites [27] Kraneveld, 2008, The cell wall of the human pathogen Candida glabrata: Differential incorporation of novel adhesin-like wall proteins, Eukaryot. Cell source

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    • cites [29] Pan, 2003, Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing, Genes Dev. source

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    • cites [30] Domergue, 2005, Nicotinic acid limitation regulates silencing of Candida adhesins during UTI, Science source

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    • cites [31] López-Fuentes, E., Gutiérrez-Escobedo, G., Timmermans, B., Van Dijck, P., De Las Peñas, A., and Castaño, I. (2018). Candida glabrata’s genome plasticity confers a unique pattern of expressed cell wall proteins. J. Fungi, 4. source

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    CgPdr1 has been implicated in regulation of EPA1 gene expression.

    “The multidrug resistance transcription factor CgPdr1 has been implicated in regulation of the EPA1 gene expression [34].”
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    • cites [34] Moeckli, 2016, Upregulation of the adhesin gene EPA1 mediated by PDR1 in Candida glabrata leads to enhanced host colonization, mSphere

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    C. glabrata biofilms display antifungal resistance and are characterized by a compact dense structure of yeast cells nested in an extracellular matrix composed of high levels of proteins and carbohydrates including β-1,3 glucan.

    “C. glabrata biofilms display antifungal resistance, and are characterized by a compact dense structure of yeast cells nested in an extracellular matrix which is composed of high levels of proteins and carbohydrates including β-1,3 glucan [50,51,52].”
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    • cites [50] Janbon, 2015, Biofilm formation in Candida glabrata: What have we learnt from functional genomics approaches?, FEMS Yeast Res.

      Not checked in the free run.

    • cites [51] Silva, 2009, Biofilms of non-Candida albicans Candida species: Quantification, structure and matrix composition, Med. Mycol. source

      Not checked in the free run.

    • cites [52] 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.

  • May combine two claims.

    Premisecitation

    The Epa sub-family I contains the PA14 ligand-binding domain, is most well studied, and consists of 17 to 23 proteins depending upon the isolate.

    “The Epa (Epithelial Adhesin) sub-family I, containing the PA14 (Anthrax Protective Antigen) ligand-binding domain, is most well studied, and consists of 17 to 23 proteins depending upon the isolate [27,28].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27] Kraneveld, 2008, The cell wall of the human pathogen Candida glabrata: Differential incorporation of novel adhesin-like wall proteins, Eukaryot. Cell source

      Not checked in the free run.

    • cites [28] Kaur, 2005, A yeast by any other name: Candida glabrata and its interaction with the host, Curr. Opin. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The presence of a large number of adhesin genes and their complex environment-dependent differential regulation are likely to help C. glabrata colonize different host niches as well as form biofilms on a wide range of surfaces.

    “Therefore, the presence of such a large number of adhesin genes and their complex environment-dependent differential regulation are likely to help C. glabrata colonize different host niches as well as to form biofilms on a wide range of surfaces [27,47,48].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [27] Kraneveld, 2008, The cell wall of the human pathogen Candida glabrata: Differential incorporation of novel adhesin-like wall proteins, Eukaryot. Cell source

      Not checked in the free run.

    • cites [47] Thierry, 2008, Megasatellites: A peculiar class of giant minisatellites in genes involved in cell adhesion and pathogenicity in Candida glabrata, Nucleic Acids Res. source

      Not checked in the free run.

    • cites [48] Beaudoing, 2017, Comparative genomics of two sequential Candida glabrata clinical isolates, G3 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Disruption of the transcription factor CgAce2 leads to cell aggregation due to defects in cell separation, and hypervirulence.

    “Furthermore, disruption of the transcription factor CgAce2 is known to lead to cell aggregation, due to defects in cell separation, and hypervirulence [72,73].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [72] Kamran, 2004, Inactivation of transcription factor gene ACE2 in the fungal pathogen Candida glabrata results in hypervirulence, Eukaryot. Cell source

      Not checked in the free run.

    • cites [73] MacCallum, 2006, Different consequences of ACE2 and SWI5 gene disruptions for virulence of pathogenic and nonpathogenic yeasts, Infect. Immun. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The mutant lacking eleven yapsins displays a large acidic vacuole, elevated metal ion susceptibility, mis-sorting of the vacuole hydrolase carboxypeptidase Y, diminished vacuolar ATPase activity and perturbed polyphosphate and energy homeostasis.

    “Additionally, the mutant lacking eleven yapsins was found to display large acidic vacuole, elevated metal ion susceptibility, mis-sorting of the vacuole hydrolase carboxypeptidase Y (CPY), diminished vacuolar ATPase activity and perturbed polyphosphate and energy homeostasis (Figure 1) [64].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Bairwa, 2014, GPI (glycosylphosphatidylinositol)-linked aspartyl proteases regulate vacuole homoeostasis in Candida glabrata, Biochem. J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CgMTL1 and CgMTL2 are transcriptionally active, while CgMTL3 is subjected to subtelomeric silencing.

    “While CgMTL1 and CgMTL2 are transcriptionally active, CgMTL3 is subjected to subtelomeric silencing [77].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [77] 2010, Subtelomeric silencing of the MTL3 locus of Candida glabrata requires yKu70, yKu80, and Rif1 proteins, Eukaryot. Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ectopic expression of the S. cerevisiae endonuclease-encoding HO gene results in efficient mating-type switching and lethality in C. glabrata.

    “However, ectopic expression of the S. cerevisiae endonuclease-encoding HO gene is known to result in efficient mating-type switching and lethality in C. glabrata [78].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [78] Boisnard, 2015, Efficient mating-type switching in Candida glabrata induces cell death, PLoS ONE source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CgYps1 is uniquely required to survive acid stress; CgYPS1 deletion led to low intracellular pH, high ROS levels and cell death under low pH and acidic environmental conditions.

    “Of eleven CgYapsins, CgYps1 is uniquely required to survive acid stress, as CgYPS1 deletion led to low intracellular pH, high ROS (reactive oxygen species) levels and cell death under low pH and acidic environmental conditions [61].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Bairwa, 2011, A novel role for a glycosylphosphatidylinositol-anchored aspartyl protease, CgYps1, in the regulation of pH homeostasis in Candida glabrata, Mol. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Despite an essential role of CgCta1 in resistance to hydrogen peroxide-generated oxidative stress in vitro, the Cgcta1Δ mutant was not attenuated for virulence in the murine disseminated candidiasis model.

    “Despite an essential role of CgCta1 in resistance to the hydrogen peroxide-generated oxidative stress in vitro, the Cgcta1Δ mutant was not attenuated for virulence in the murine disseminated candidiasis model which suggests the existence of a CgCta1-independent resistance mechanism in vivo [80].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [80] 2008, High resistance to oxidative stress in the fungal pathogen Candida glabrata is mediated by a single catalase, Cta1p, and is controlled by the transcription factors Yap1p, Skn7p, Msn2p, and Msn4p, Eukaryot. Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CgYapsins suppress production of pro-inflammatory cytokine IL-1β in human THP-1 macrophages, facilitate survival in macrophages and virulence in the models of murine systemic candidiasis and Drosophila melanogaster.

    “The latter includes suppression of the production of pro-inflammatory cytokine IL-1β in human THP-1 macrophages, facilitating survival in macrophages and virulence in the models of murine systemic candidiasis and Drosophila melanogaster [58,60,65,66].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [58] Rasheed, 2018, Aspartyl proteases in Candida glabrata are required for suppression of the host innate immune response, J. Biol. Chem. source

      Not checked in the free run.

    • cites [60] Kaur, 2007, A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

    • cites [65] Seider, 2011, The facultative intracellular pathogen Candida glabrata subverts macrophage cytokine production and phagolysosome maturation, J. Immunol. source

      Not checked in the free run.

    • cites [66] Quintin, 2013, The Drosophila toll pathway controls but does not clear Candida glabrata infections, J. Immunol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CgYapsins are implicated in shedding Epa1 adhesin off the cell wall; Epa1 release into the medium was drastically reduced in the Cgyps1-11Δ mutant compared to wild-type cells.

    “CgYapsins have also been implicated in shedding Epa1 adhesin off the cell wall, as Epa1 release into the medium was drastically reduced in the Cgyps1-11Δ mutant compared to wild-type cells (Figure 1) [60].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Kaur, 2007, A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Cgyps1-11Δ mutant displays sunken cell walls containing higher chitin and reduced β-glucan and mannan levels.

    “Lastly, the Cgyps1-11Δ mutant displayed sunken cell walls containing higher chitin and reduced β-glucan and mannan levels (Figure 1) [58,64].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [58] Rasheed, 2018, Aspartyl proteases in Candida glabrata are required for suppression of the host innate immune response, J. Biol. Chem. source

      Not checked in the free run.

    • cites [64] Bairwa, 2014, GPI (glycosylphosphatidylinositol)-linked aspartyl proteases regulate vacuole homoeostasis in Candida glabrata, Biochem. J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Genomic recombination between different clades and evidence for an active sexual cycle have recently been reported in C. glabrata.

    “Of note, genomic recombination between different clades and evidence for an active sexual cycle have recently been reported in C. glabrata [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Ksiezopolska, 2018, Patterns of genomic variation in the opportunistic pathogen Candida glabrata suggest the existence of mating and a secondary association with humans, Curr. Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Switching between these colony phenotypes is common, spontaneous and reversible.

    “Switching between these phenotypes, that was found to be common, spontaneous and reversible [68], had also been shown to occur at sites of colonization in vaginitis patients [69].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Lachke, 2002, Phenotypic switching and filamentation in Candida glabrata, Microbiology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nicotinic acid auxotrophy is a trait of the Nakaseomyces clade, which contains both environmental and pathogenic species.

    “The loss of nicotinic acid synthesis genes was thought to be due to close association of C. glabrata with the mammalian host, however, recent studies report that the nicotinic acid auxotrophy is a trait of the Nakaseomyces clade, which contains both environmental and pathogenic species [18].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The high osmolarity glycerol pathway is activated by sorbic acid, and its terminal MAPK CgHog1 is required for survival of weak acid and osmotic stress.

    “However, the high osmolarity glycerol pathway [HOG] is known to be activated by sorbic acid, and its terminal MAPK CgHog1 is required for survival of weak acid and osmotic stress [95,96].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [95] Jandric, 2013, Sorbic acid stress activates the Candida glabrata high osmolarity glycerol MAP kinase pathway, Front. Microbiol. source

      Not checked in the free run.

    • cites [96] Srivastava, 2015, The mitogen-activated protein kinase CgHog1 is required for iron homeostasis, adherence and virulence in Candida glabrata, FEBS J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Deletion of the transcriptional co-activator CgAda2 conferred resistance to the ER stressor tunicamycin and hypervirulence in immunocompromised mice.

    “Contrarily, deletion of the transcriptional co-activator CgAda2 conferred resistance to the ER stressor, tunicamycin, and hypervirulence in the immunocompromised mice [98].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Yu, 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

    C. glabrata is able to grow in very low concentration of glucose, and its glucose sensing pathway resembles that of S. cerevisiae.

    “C. glabrata is also able to grow in very low concentration of glucose, and its glucose sensing pathway resembles to that of S. cerevisiae [113].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [113] Ng, 2015, SNF3 as high affinity glucose sensor and its function in supporting the viability of Candida glabrata under glucose-limited environment, Front. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. glabrata can assimilate both glucose and trehalose, but lacks genes for assimilation of galactose and sucrose.

    “C. glabrata can assimilate both glucose and trehalose, but lacks genes for assimilation of galactose and sucrose [17,28].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] Dujon, 2004, Genome evolution in yeasts, Nature source

      Not checked in the free run.

    • cites [28] Kaur, 2005, A yeast by any other name: Candida glabrata and its interaction with the host, Curr. Opin. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The protein kinase C (PKC)-mediated signaling pathway safeguards the cell wall in C. glabrata, and its terminal mitogen-activated protein kinase CgSlt2, along with other cascade components, is required for survival of cell wall stress.

    “The protein kinase C (PKC)-mediated signaling pathway safeguards the cell wall in C. glabrata, and its terminal mitogen-activated protein kinase (MAPK) CgSlt2, along with other cascade components, is required for survival of the cell wall stress [54,90,91].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [54] Schwarzmuller, T., Ma, B., Hiller, E., Istel, F., Tscherner, M., Brunke, S., Ames, L., Firon, A., Green, B., and Cabral, V. (2014). Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes. PLoS Pathog., 10. source

      Not checked in the free run.

    • cites [90] Miyazaki, 2010, Role of the Slt2 mitogen-activated protein kinase pathway in cell wall integrity and virulence in Candida glabrata, FEMS Yeast Res. source

      Not checked in the free run.

    • cites [91] Borah, 2011, The Rho1 GTPase-activating protein CgBem2 is required for survival of azole stress in Candida glabrata, J. Biol. Chem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. glabrata is a facultatively anaerobic, crabtree-positive yeast which prefers fermentation over respiration in the presence of oxygen.

    “C. glabrata is a facultatively anaerobic, crabtree-positive yeast which prefers fermentation over respiration in the presence of oxygen [110,111].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [110] Voll, 1990, Transient-state analysis of metabolic fluxes in crabtree-positive and crabtree-negative yeasts, Appl. Environ. Microbiol. source

      Not checked in the free run.

    • cites [111] Legrand, 2016, Life-history strategies and carbon metabolism gene dosage in the Nakaseomyces yeasts, FEMS Yeast Res. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    C. glabrata has rewired its metabolic machinery and developed novel nutrient uptake mechanisms.

    “C. glabrata has rewired its metabolic machinery, and developed novel nutrient uptake mechanisms.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The ability to acquire nutrition from the nutrient-limited host environment is a prerequisite to thrive in the host.

  • May combine two claims.

    Premisecitation

    C. glabrata has lost 5, 4, 3, 3 and 6 genes involved in galactose metabolism, phosphate metabolism, cell rescue, defense and virulence, nitrogen and sulfur metabolism, and allantoin catabolism, respectively.

    “It has lost 5, 4, 3, 3 and 6 genes involved in galactose metabolism, phosphate metabolism, cell rescue, defense and virulence, nitrogen and sulfur metabolism, and allantoin catabolism, respectively [17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Dujon, 2004, Genome evolution in yeasts, Nature source

      Not checked in the free run.

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

    Premisecitation

    Tryptophan-based pigment production aids in survival of ROS stress.

    “Furthermore, tryptophan-based pigment production is also known to aid in survival of the ROS stress [89].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [89] Brunke, 2010, Candida glabrata tryptophan-based pigment production via the Ehrlich pathway, Mol. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CgSnf3 acts as the high-affinity glucose sensor which is essential for growth under glucose-limited conditions and in macrophages.

    “CgSnf3 acts as the high-affinity glucose sensor which is essential for growth under glucose-limited conditions and in macrophages [113].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [113] Ng, 2015, SNF3 as high affinity glucose sensor and its function in supporting the viability of Candida glabrata under glucose-limited environment, Front. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. glabrata exhibits haemolytic activity in vitro and possesses hemolysins.

    “Although C. glabrata exhibits haemolytic activity in vitro and possesses hemolysins, it lacks the haem receptor [121,122,124].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [121] Weissman, 2004, A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization, Mol. Microbiol. source

      Not checked in the free run.

    • cites [122] 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.

    • cites [124] Luo, 2001, Candida species exhibit differential in vitro hemolytic activities, J. Clin. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. glabrata has a set of six conserved duplicated gene paralogs encoding glycolytic enzymes, Eno1/Eno2, Pyc1/Pyc2, Glk1/Emi2, Hxk1/Hxk2, Tdh2/Tdh3 and Cdc19/Pyk2, that may aid in increased carbon flux through glycolysis and contribute to its respiro-fermentative lifestyle.

    “C. glabrata also has a set of six conserved duplicated gene paralogs encoding glycolytic enzymes, Eno1/Eno2, Pyc1/Pyc2, Glk1/Emi2, Hxk1/Hxk2, Tdh2/Tdh3 and Cdc19/Pyk2 [18], that may aid in the increased carbon flux through glycolysis, and contribute to its respiro-fermentative lifestyle [114].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Gabaldón, T., Martin, T., Marcet-Houben, M., Durrens, P., Bolotin-Fukuhara, M., Lespinet, O., Arnaise, S., Boisnard, S., Aguileta, G., and Atanasova, R. (2013). Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics, 14. source

      Not checked in the free run.

    • cites [114] Conant, 2007, Increased glycolytic flux as an outcome of whole-genome duplication in yeast, Mol. Syst. Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CgPMU2 transcript levels are lower in high-phosphate conditions and substantially higher during phosphate starvation.

    “Consistent with this, CgPMU2 transcript levels were lower in high-phosphate conditions and substantially higher during phosphate starvation [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Orkwis, 2010, Novel acid phosphatase in Candida glabrata suggests selective pressure and niche specialization in the phosphate signal transduction pathway, Genetics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CgPmu3 is a thiamine phosphatase that is transcriptionally regulated by CgThi3 in response to thiamine starvation.

    “Recently, CgPmu3 has been shown to be a thiamine phosphatase that is transcriptionally regulated by the transcription factor CgThi3 in response to thiamine starvation [119].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [119] Nahas, 2018, Dynamic changes in yeast phosphatase families allow for specialization in phosphate and thiamine starvation, G3 source

      Not checked in the free run.

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

    Premisecitation

    Neutrophils are major players of the host defense system against fungal infections.

    “Neutrophils are major players of the host defense system against fungal infections [140].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [140] Netea, 2015, Immune defense against Candida fungal infections, Nat. Rev. Immunol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CgPWP7 and CgAED1 are not transcriptionally regulated by silencing.

    “However, unlike EPA genes, CgPWP7 and CgAED1 were not transcriptionally regulated by silencing [23].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Desai, 2011, Candida glabrata Pwp7p and Aed1p are required for adherence to human endothelial cells, FEMS Yeast Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Three bZip transcription factors, CgYap1, CgYap5, and CgYap7, have been implicated in regulation of heme biosynthesis, iron-excess stress response, and iron-sulfur cluster biogenesis, respectively.

    “Of note, three bZip transcription factors, CgYap1, CgYap5 and CgYap7 have also been implicated in regulation of the heme biosynthesis, iron-excess stress response and iron-sulfur cluster biogenesis, respectively [127].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] Merhej, 2016, A network of paralogous stress response transcription factors in the human pathogen Candida glabrata, Front. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The C. glabrata Cgsir3Δ mutant displays mannose- and galactose-dependent strong binding to the coronary endothelium through coronary endothelial luminal membrane lectinic GPCRs including endothelin-2 and α-adrenergic 1A receptor, leading to altered cardiac functions.

    “The C. glabrata Cgsir3Δ mutant, which expresses higher levels of Epa adhesins [36], has been reported to display mannose- and galactose-dependent strong binding to the coronary endothelium, through the coronary endothelial luminal membrane lectinic G protein-coupled receptors (GPCRs) including endothelin-2 and α-adrenergic 1A receptor, that led to altered cardiac functions [139].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [139] Knabb, 2016, Candida glabrata binds to glycosylated and lectinic receptors on the coronary endothelial luminal membrane and inhibits flow sense and cardiac responses to agonists, Am. J. Physiol. Regul. Integr. Comp. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Lack of CgHog1 resulted in elevated intracellular iron and mitochondrial iron content and cell death in the high-iron environment.

    “With regard to signaling pathways, Hog1-mediated MAPK has been shown to be essential for survival under high iron stress, as a lack of CgHog1 resulted in elevated intracellular iron and mitochondrial iron content and cell death in the high-iron environment [96].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [96] Srivastava, 2015, The mitogen-activated protein kinase CgHog1 is required for iron homeostasis, adherence and virulence in Candida glabrata, FEBS J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. glabrata survives and replicates in human and murine macrophages without adversely affecting macrophages.

    “C. glabrata survives and replicates in human and murine macrophages without adversely affecting macrophages [60,65,147].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [60] Kaur, 2007, A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

    • cites [65] Seider, 2011, The facultative intracellular pathogen Candida glabrata subverts macrophage cytokine production and phagolysosome maturation, J. Immunol. source

      Not checked in the free run.

    • cites [147] Rai, M.N., Balusu, S., Gorityala, N., Dandu, L., and Kaur, R. (2012). Functional genomic analysis of candida glabrata-macrophage interaction: Role of chromatin remodeling in virulence. PLoS Pathog., 8. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Murine dendritic cells produce IFN-β through the toll-like receptor TLR7, underscoring the role of IFN-I signaling in modulation of the host response to C. glabrata infection.

    “Additionally, the murine dendritic cells have also been reported to produce IFN-β through the toll-like receptor TLR7, thereby, underscoring the role of IFN-I signaling in modulation of the host response to C. glabrata infection [146].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [146] Bourgeois, 2011, Conventional dendritic cells mount a Type I IFN response against Candida spp. requiring novel phagosomal TLR7-mediated IFN- Signaling, J. Immunol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. glabrata activates pexophagy and autophagy processes.

    “C. glabrata activates pexophagy and autophagy processes, undergoes chromatin remodeling and evades immune responses to survive and replicate in macrophages [84,147,150].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [84] Roetzer, 2010, Autophagy supports Candida glabrata survival during phagocytosis, Cell. Microbiol. source

      Not checked in the free run.

    • cites [147] Rai, M.N., Balusu, S., Gorityala, N., Dandu, L., and Kaur, R. (2012). Functional genomic analysis of candida glabrata-macrophage interaction: Role of chromatin remodeling in virulence. PLoS Pathog., 8. source

      Not checked in the free run.

    • cites [150] Seider, 2014, Immune evasion, stress resistance, and efficient nutrient acquisition are crucial for intracellular survival of Candida glabrata within macrophages, Eukaryot. Cell source

      Not checked in the free run.

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

    Premisecitation

    Macrophages are the primary effectors of the innate immune system.

    “Macrophages are the primary effectors of the innate immune system [140].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [140] Netea, 2015, Immune defense against Candida fungal infections, Nat. Rev. Immunol. source

      Not checked in the free run.

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

    Interpretationnone given

    C. glabrata occupies a unique position in the phylogenetic tree and appears to possess requisite attributes to establish successful infections in the human host.

    “C. glabrata occupies a unique position in the phylogenetic tree and appears to possess requisite attributes to establish successful infections in the human host.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    Owing to its reduced susceptibility to azole antifungals and emerging resistance to echinocandins, effective treatment of C. glabrata infections remains a clinical challenge.

    “Owing to its reduced susceptibility to azole antifungals and emerging resistance to echinocandins, effective treatment of C. glabrata infections remains a clinical challenge.”
    Quote in the paperNot a substantial claim
64 of 64

  • The paper relies on this without support.

    Adherence to host tissue is an important trait that contributes to colonization and establishment of successful infections.

    “Adherence to the host tissue is an important trait that contributes to colonization and establishment of successful infections.”

  • The paper relies on this without support.

    The ability to acquire nutrition from the nutrient-limited host environment is a prerequisite to thrive in the host.

    “A prerequisite to thrive in the host is the ability to acquire nutrition from the nutrient-limited host environment.”

  • The authors state this as an assumption.

    C. glabrata and S. cerevisiae arose from the same tetraploid hybrid ancestor about 100-200 million years ago.

    “Both C. glabrata and S. cerevisiae belong to the Whole Genome Duplication (WGD) group, and are assumed to have arisen from the same tetraploid hybrid ancestor, which existed about 100-200 million years ago [18].”

  • The authors state this as an assumption.

    Macrophages are Trojan horses for C. glabrata.

    “Altogether, because of its ability to subvert the immune response and replicate in macrophages in vitro, macrophages are assumed to be the Trojan horses for C. glabrata [58,143,151].”

  • The paper relies on this without support.

    Adhesion of C. glabrata to epithelial cells and extracellular matrix is a prerequisite for mucosal colonization.

    “Adhesion of C. glabrata to epithelial cells and extracellular matrix is a prerequisite for mucosal colonization.”
5 of 5

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

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Cited by

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Related

Authors
Kumar, K., Askari, F., Sahu, M. S., & Kaur, R.
Affiliations
  • Manipal Academy of Higher Education (IN)
  • Regional Centre for Biotechnology (IN)
  • Centre for DNA Fingerprinting and Diagnostics (IN)
Corresponding author
Kaur, Rupinder
ORCID
Venue
Microorganisms
Publisher
MDPI AG
Published
2019-01-30
Volume
7
Issue
2
Pages
39
ISSN
2076-2607 (ISSN-L)
DOI
10.3390/microorganisms7020039
PMC
PMC6407134
OpenAlex
W2913634472
Semantic Scholar
97cde065e909ebe37da61a163e4d66d783bbb373
Cited by
128
References
153
Citations by year
2026: 14 · 2025: 9 · 2024: 12 · 2023: 29 · 2022: 21 · 2021: 19 · 2020: 19 · 2019: 5
FWCI
2.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Microorganisms (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • DBT India Alliance (IA/S/15/1/501831)
  • Department of Biotechnology , Ministry of Science and Technology (BT/HRD/NBA/37/01/2014)
  • Science and Engineering Research Board (EMR/2016/005375)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida glabrata, opportunistic fungal infection, bloodstream infection, host-pathogen interaction, iron acquisition, phosphate acquisition, cell surface adhesins, aspartic protease, biofilm formation, stress response, virulence factors, macrophage evasion, intracellular replication, immune evasion

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 ›

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