Functional analysis of <i>Candida albicans</i> genes whose <i>Saccharomyces cerevisiae</i> homologues are involved in endocytosis

Martin, Ronny; Hellwig, Daniela; Schaub, Yvonne; Bauer, Janine; Walther, Andrea; Wendland, Jürgen

doi:10.1002/yea.1489

Cited by 31 publications

(39 citation statements)

References 42 publications

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“…Likewise, a role for endocytosis in C. albicans hyphal growth had been suggested by the requirement for proteins involved in fluid phase endocytosis such as Pan1 81 , myosin type I Myo5 82 , the Wiscott-Aldrich Syndrome Protein homolog Wal1 83 , the verprolin Vrp1 84 , and the BAR domain proteins Rvs161 and Rvs167 85 . The likely explanation for a requirement for endocytosis in hyphal morphogenesis is the need to recycle membranes as well as membrane proteins deposited by vesicle exocytosis at the tip of the extending hypha (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis

Bar-Yosef

Gonzalez

Ben-Aroya

et al. 2017

Sci Rep

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Candida albicans is an opportunistic pathogen, typically found as a benign commensal yeast living on skin and mucosa, but poised to invade injured tissue to cause local infections. In debilitated and immunocompromised individuals, C. albicans may spread to cause life-threatening systemic infections. Upon contact with serum and at body temperature, C. albicans performs a regulated switch to filamentous morphology, characterized by emergence of a germ tube from the yeast cell followed by mold-like growth of branching hyphae. The ability to switch between growth morphologies is an important virulence factor of C. albicans. To identify compounds able to inhibit hyphal morphogenesis, we screened libraries of existing drugs for inhibition of the hyphal switch under stringent conditions. Several compounds that specifically inhibited hyphal morphogenesis were identified. Chemogenomic analysis suggested an interaction with the endocytic pathway, which was confirmed by direct measurement of fluid-phase endocytosis in the presence of these compounds. These results suggest that the activity of the endocytic pathway, which is known to be particularly important for hyphal growth, represents an effective target for hyphae-inhibiting drugs.

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Section: Discussionmentioning

confidence: 99%

Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis

Bar-Yosef

Gonzalez

Ben-Aroya

et al. 2017

Sci Rep

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“…Previously, C. albicans ORFs homologous to S. cerevisiae endocytosis genes were investigated for their involvement in polarized cell growth [32]. Specifically, the authors examined ABP1 , BZZ1 , EDE1 , and PAN1 , whose gene products are involved in the early stages of endocytosis [33].…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, the authors examined ABP1 , BZZ1 , EDE1 , and PAN1 , whose gene products are involved in the early stages of endocytosis [33]. Loss of function of PAN1 , but not ABP1 , BZZ1 , or EDE1 , resulted in altered hyphal formation [32]. More recently, Douglas et al [34] investigated the role of C. albicans RVS161 and RVS167 whose homologues in S. cerevisiae are involved in the severance of budding endocytic vesicles from the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Candida albicans SUR7 contributes to secretion, biofilm formation, and macrophage killing

Bernardo

Lee

2010

BMC Microbiol

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BackgroundCandida albicans SUR7 has been shown to be required for plasma membrane organization and cell wall synthesis, but its role in virulence is not known. Using a bioinformatics strategy, we previously identified several novel putative secretion pathway proteins potentially involved in virulence, including the C. albicans homolog of the Saccharomyces cerevisiae endocytosis-related protein Sur7p. We therefore generated a C. albicans sur7Δ null mutant and examined its contribution to key virulence attributes.ResultsStructurally, the C. albicans sur7Δ mutant was impaired in response to filamentation-inducing conditions, and formed aberrant hyphae with extensive accumulation of plasma membrane-derived structures within the cell. Absence of SUR7 resulted in a temperature-sensitive growth defect at high temperatures (42°C), which was partially rescued by addition of NaCl. We next examined the role of the SUR7 paralog C. albicans FMP45 in this temperature-sensitive phenotype. Analysis of C. albicans Fmp45p-GFP demonstrated co-localization of Fmp45p with Sur7p and increased fluorescence in the plasma membrane in the presence of high salt. We next focused on key virulence-related phenotypes. The C. albicans sur7Δ null mutant exhibited secretory defects: reduced lipase secretion, and increased levels of secreted Sap2p. The null mutant was hyper-susceptible to sub-inhibitory concentrations of caspofungin, but not amphotericin B and 5-fluorocytosine. Functionally, the sur7Δ mutant demonstrated increased adhesion to polystyrene and of note, was markedly defective in biofilm formation. In an in vitro macrophage model of virulence, the sur7Δ mutant was impaired in macrophage killing.ConclusionsPlasma membrane and cell wall organization are important for cell morphology, and alterations of these structures contributed to impairment of several key virulence-associated phenotypes in the C. albicans sur7Δ mutant.

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“…As with many other molecular systems, S. cerevisiae has continued to serve as the model from which analogous conclusions are derived. In a study of C. albicans ORFs whose homologs in S. cerevisiae are involved in endocytosis, several genes encoding endocytic coat components, such as Ede1 and the adaptor protein Pan1, were found [48]. An actin-binding protein, Abp1, and a marker for actin polymerization in cortical patches, Bzz1, that are involved in endocytosis of C. albicans were also found [48 – 50].…”

Section: Secretory Transport Is Linked To Virulence Of Candida Albicansmentioning

confidence: 99%

“…In a study of C. albicans ORFs whose homologs in S. cerevisiae are involved in endocytosis, several genes encoding endocytic coat components, such as Ede1 and the adaptor protein Pan1, were found [48]. An actin-binding protein, Abp1, and a marker for actin polymerization in cortical patches, Bzz1, that are involved in endocytosis of C. albicans were also found [48 – 50]. C. albicans Ede1 is similar to yeast Ede1 by containing three EH domains [48] and End3 is also similar to the yeast homolog that binds to Pan1 [51].…”

Section: Secretory Transport Is Linked To Virulence Of Candida Albicansmentioning

confidence: 99%

The endocytic adaptor proteins of pathogenic fungi: charting new and familiar pathways

Wang¹,

Shen²

2011

Med Mycol

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Intracellular transport is an essential biological process that is highly conserved throughout the eukaryotic organisms. In fungi, adaptor proteins implicated in the endocytic cycle of endocytosis and exocytosis were found to be important for growth, differentiation, and/or virulence. For example, Saccharomyces cerevisiae Pan1 is an endocytic protein that regulates membrane trafficking, the actin cytoskeleton, and signaling. In Cryptococcus neoformans, a multi-modular endocytic protein, Cin1, was recently found to have pleiotropic functions in morphogenesis, endocytosis, exocytosis, and virulence. Interestingly, Cin1 is homologous to human intersectin ITSN1, but homologs of Cin1/ITSN1 were not found in ascomycetous S. cerevisiae and Candida albicans, or zygomycetous fungi. Moreover, an Eps15 protein homologous to S. cerevisiae Pan1/Ede1 and additional relevant protein homologs were identified in C. neoformans, suggesting the existence of either a distinct endocytic pathway mediated by Cin1 or pathways by either Cin1 or/and Pan1/Ede1 homologs. Whether and how the Cin1-mediated endocytic pathway represents a unique role in pathogenesis or reflects a redundancy of a transport apparatus remains an open and challenging question. This review discusses recent findings of endocytic adaptor proteins from pathogenic fungi and provides a perspective for novel endocytic machinery operating in C. neoformans. An understanding of intracellular trafficking mechanisms as they relate to pathogenesis will likely reveal the identity of novel antifungal targets.

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Functional analysis of Candida albicans genes whose Saccharomyces cerevisiae homologues are involved in endocytosis

Cited by 31 publications

References 42 publications

Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis

Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis

Candida albicans SUR7 contributes to secretion, biofilm formation, and macrophage killing

The endocytic adaptor proteins of pathogenic fungi: charting new and familiar pathways

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