New regulators of biofilm development in Candida glabrata

Riera, Marta; Mogensen, Estelle; d’Enfert, Christophe; Janbon, Guilhem

doi:10.1016/j.resmic.2012.02.005

Cited by 39 publications

(49 citation statements)

References 54 publications

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“…Biofilm formation on indwelling medical devices represents a significant risk for invasive infections by Candida spp , since biofilms display both increased drug tolerance and represent a persistent source of shedded cells that disseminate via the blood stream [71]–[73]. Hence, mutants in the deletion collection were scored for their ability to form biofilms.…”

Section: Resultsmentioning

confidence: 99%

Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes

et al. 2014

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The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes.

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Section: Resultsmentioning

confidence: 99%

Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes

et al. 2014

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“…C. glabrata has the capacity to adhere to other cells, such as phagocytic or epithelial cells, but also to abiotic surfaces, such as catheters, prosthesis or other medical artificial material implanted in the human body (Cowen et al, ), forming biofilms (Roetzer, Gabaldón, & Schüller, ). These cellular structures have been associated with higher tolerance to antifungals and to increased colonization/infection and persistence (Riera, Mogensen, D'Enfert, & Janbon, ).…”

Section: Resultsmentioning

confidence: 99%

The multidrug resistance transporters CgTpo1_1 and CgTpo1_2 play a role in virulence and biofilm formation in the human pathogenCandida glabrata

Santos

Costa

Mil‐Homens

et al. 2017

Cellular Microbiology

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The mechanisms of persistence and virulence associated with Candida glabrata infections are poorly understood, limiting the ability to fight this fungal pathogen. In this study, the multidrug resistance transporters CgTpo1_1 and CgTpo1_2 are shown to play a role in C. glabrata virulence. The survival of the infection model Galleria mellonella, infected with C. glabrata, was found to increase upon the deletion of either CgTPO1_1 or CgTPO1_2. The underlying mechanisms were further explored. In the case of CgTpo1_1, this phenotype was found to be consistent with the observation that it confers resistance to antimicrobial peptides (AMP), such as the human AMP histatin-5. The deletion of CgTPO1_2, on the other hand, was found to limit the survival of C. glabrata cells when exposed to phagocytosis and impair biofilm formation. Interestingly, CgTPO1_2 expression was found to be up-regulated during biofilm formation, but and its deletion leads to a decreased expression of adhesin-encoding genes during biofilm formation, which is consistent with a role in biofilm formation. CgTPO1_2 expression was further seen to decrease plasma membrane potential and affect ergosterol and fatty acid content. Altogether, CgTpo1_1 and CgTpo1_2 appear to play an important role in the virulence of C. glabrata infections, being at the cross-road between multidrug resistance and pathogenesis.

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“…8,9 Use of a genetic screening strategy enabled to identify Epa6 as the principal adhesin involved in biofilm formation. 8,9 To date, the molecular interactions involved in Epa6-mediated adhesion are not established. Clearly, enhancing our understanding of Epa6-dependent interactions may contribute to the development of novel strategies for combating biofilm infections.…”

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confidence: 99%

Force Nanoscopy of Hydrophobic Interactions in the Fungal Pathogen Candida glabrata

et al. 2015

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Candida glabrata is an opportunistic human fungal pathogen which binds to surfaces mainly through the Epa family of cell adhesion proteins. While some Epa proteins mediate specific lectin-like interactions with human epithelial cells, others promote adhesion and biofilm formation on plastic surfaces via nonspecific interactions that are not yet elucidated. We report the measurement of hydrophobic forces engaged in Epa6-mediated cell adhesion by means of atomic force microscopy (AFM). Using single-cell force spectroscopy, we found that C. glabrata wild-type (WT) cells attach to hydrophobic surfaces via strongly adhesive macromolecular bonds, while mutant cells impaired in Epa6 expression are weakly adhesive. Nanoscale mapping of yeast cells using AFM tips functionalized with hydrophobic groups shows that Epa6 is massively exposed on WT cells and conveys strong hydrophobic properties to the cell surface. Our results demonstrate that Epa6 mediates strong hydrophobic interactions, thereby providing a molecular basis for the ability of this adhesin to drive biofilm formation on abiotic surfaces.

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New regulators of biofilm development in Candida glabrata

Cited by 39 publications

References 54 publications

Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes

Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes

The multidrug resistance transporters CgTpo1_1 and CgTpo1_2 play a role in virulence and biofilm formation in the human pathogenCandida glabrata

Force Nanoscopy of Hydrophobic Interactions in the Fungal Pathogen Candida glabrata

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