Candida albicans Vrp1 is required for polarized morphogenesis and interacts with Wal1 and Myo5

Borth, Nicole; Walther, Andrea; Reijnst, Patrick; Jorde, Sigyn; Schaub, Yvonne; Wendland, Jürgen

doi:10.1099/mic.0.041707-0

Cited by 16 publications

(17 citation statements)

References 40 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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“…Given that Spider medium was originally used to induce a/␣ yeast cells to extend germ tubes, which elongate to form compartmentalized hyphae (52)(53)(54)(55)(56)(57)(58)(59), it was no surprise to find that the addition of a/␣ yeast cells from the stationary phase of planktonic cultures to this medium resulted in germ tube formation by a majority of the cells that had adhered to the substrate after 90 min. These germ tubes subsequently grew into narrow, long hyphae.…”

Section: Discussionmentioning

confidence: 99%

Impact of Environmental Conditions on the Form and Function of Candida albicans Biofilms

et al. 2013

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Candida albicans, like other pathogens, can form complex biofilms on a variety of substrates. However, as the number of studies of gene regulation, architecture, and pathogenic traits of C. albicans biofilms has increased, so have differences in results. This suggests that depending upon the conditions employed, biofilms may vary widely, thus hampering attempts at a uniform description. Gene expression studies suggest that this may be the case. To explore this hypothesis further, we compared the architectures and traits of biofilms formed in RPMI 1640 and Spider media at 37°C in air. Biofilms formed by a/␣ cells in the two media differed to various degrees in cellular architecture, matrix deposition, penetrability by leukocytes, fluconazole susceptibility, and the facilitation of mating. Similar comparisons of a/a cells in the two media, however, were made difficult given that in air, although a/a cells form traditional biofilms in RPMI medium, they form polylayers composed primarily of yeast cells in Spider medium. These polylayers lack an upper hyphal/matrix region, are readily penetrated by leukocytes, are highly fluconazole susceptible, and do not facilitate mating. If, however, air is replaced with 20% CO 2 , a/a cells make a biofilm in Spider medium similar architecturally to that of a/␣ cells, which facilitates mating. A second, more cursory comparison is made between the disparate cellular architectures of a/a biofilms formed in air in RPMI and Lee's media. The results demonstrate that C. albicans forms very different types of biofilms depending upon the composition of the medium, level of CO 2 in the atmosphere, and configuration of the MTL locus.T he opportunistic fungal pathogen Candida albicans, like opportunistic bacterial pathogens (1, 2), forms biofilms on the surfaces of a variety of tissues and synthetic devices introduced into hosts (3-5). Traditionally, biofilms serve the purpose of anchoring populations of pathogens to a surface and providing a conditioned microenvironment that facilitates growth, survival, and intercellular signaling (6, 7). Biofilms also serve to exclude host and therapeutic challenges, such as antibodies, white blood cells, and antibiotics (8, 9). Bacterial biofilms, which were initially the most intensely studied, have been shown to be architecturally complex, adhering at their base to a targeted surface and composed of multiple cell types embedded in a self-generated complex extracellular matrix (10, 11). Many of the characteristics of bacterial biofilms have been shown to be exhibited by biofilms formed by C. albicans, including drug resistance (12-15), impermeability to low-and high-molecular-weight molecules (15), and resistance to penetration by human polymorphonuclear leukocytes (PMNs) (15, 16). However, studies both to characterize the traits of C. albicans biofilms and to elucidate the molecular mechanisms regulating formation do not always provide the same results, most notably transcription profiles, mutational analyses of the signal transduction pathways, and t...

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“…Outstanding was the repression of the gene coding for a Wiskott-Aldrich syndrome protein-interacting protein, WIP/VRP. Vrp1 is important for polarized growth and polarization of actin filaments by interaction with myosin motor proteins for endocytosis in C. albicans (53) and S. cerevisiae (54). The Ras1 phenotype in growth direction maintenance can be linked (albeit not phenotypically in S. commune) to actin mislocation.…”

Section: Discussionmentioning

confidence: 99%

A Central Role for Ras1 in Morphogenesis of the Basidiomycete Schizophyllum commune

et al. 2013

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cFungi have been used as model systems to define general processes in eukaryotes, for example, the one gene-one enzyme hypothesis, as well as to study polar growth or pathogenesis. Here, we show a central role for the regulator protein Ras in a mushroomforming, filamentous basidiomycete linking growth, pheromone signaling, sexual development, and meiosis to different signal transduction pathways. ras1 and Ras-specific gap1 mutants were generated and used to modify the intracellular activation state of the Ras module. Transformants containing constitutive ras1 alleles (ras1 G12V and ras1 Q61L ), as well as their compatible mating interactions, did show strong phenotypes for growth (associated with Cdc42 signaling) and mating (associated with mitogenactivated protein kinase signaling). Normal fruiting bodies with abnormal spores exhibiting a reduced germination rate were produced by outcrossing of these mutant strains. Homozygous ⌬gap1 primordia, expected to experience increased Ras signaling, showed overlapping phenotypes with a block in basidium development and meiosis. Investigation of cyclic AMP (cAMP)-dependent protein kinase A indicated that constitutively active ras1, as well as ⌬gap1 mutant strains, exhibit a strong increase in Tpk activity. Ras1-dependent, cAMP-mediated signal transduction is, in addition to the known signaling pathways, involved in fruiting body formation in Schizophyllum commune. To integrate these analyses of Ras signaling, microarray studies were performed. Mutant strains containing constitutively active Ras1, deletion of RasGap1, or constitutively active Cdc42 were characterized and compared. At the transcriptome level, specific regulation highlighting the phenotypic differences of the mutants is clearly visible.

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Candida albicans Vrp1 is required for polarized morphogenesis and interacts with Wal1 and Myo5

Cited by 16 publications

References 40 publications

Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis

Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis

Impact of Environmental Conditions on the Form and Function of Candida albicans Biofilms

A Central Role for Ras1 in Morphogenesis of the Basidiomycete Schizophyllum commune

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