Candida albicans ENT2 Contributes to Efficient Endocytosis, Cell Wall Integrity, Filamentation, and Virulence
Autor: | Samuel A. Lee, Christiane Rollenhagen, Harrison N. Agyeman, Susan K. Eszterhas |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Epsin
Antifungal Agents Saccharomyces cerevisiae Proteins Mutant Endocytic cycle Antifungal drug Hyphae Endocytosis Microbiology biofilm Fungal Proteins Cell Wall parasitic diseases Candida albicans Humans Molecular Biology biology Virulence pathogenesis membrane trafficking Candidiasis biology.organism_classification Corpus albicans QR1-502 Cell biology filamentation secretion Adaptor Proteins Vesicular Transport Endocytic vesicle Biofilms Research Article |
Zdroj: | mSphere mSphere, Vol 6, Iss 5 (2021) |
ISSN: | 2379-5042 |
Popis: | Epsins play a pivotal role in the formation of endocytic vesicles and potentially provide a linkage between endocytic and other trafficking pathways. We identified a Candida albicans epsin, ENT2, that bears homology to the Saccharomyces cerevisiae early endocytosis genes ENT1 and ENT2 and studied its functions by a reverse genetic approach utilizing CRISPR-Cas9-mediated gene deletion. The C. albicans ent2Δ/Δ null mutant displayed cell wall defects and altered antifungal drug sensitivity. To define the role of C. albicans ENT2 in endocytosis, we performed assays with the lipophilic dye FM4-64 that revealed greatly reduced uptake in the ent2Δ/Δ mutant. Next, we showed that the C. albicans ent2Δ/Δ mutant was unable to form hyphae and biofilms. Assays for virulence properties in an in vitro keratinocyte infection model demonstrated reduced damage of mammalian adhesion zippers and host cell death from the ent2Δ/Δ mutant. We conclude that C. albicans ENT2 has a role in efficient endocytosis, a process that is required for maintaining cell wall integrity, hyphal formation, and virulence-defining traits. IMPORTANCE The opportunistic fungal pathogen Candida albicans is an important cause of invasive infections in hospitalized patients and a source of considerable morbidity and mortality. Despite its clinical importance, we still need to improve our ability to diagnose and treat this common pathogen. In order to support these advancements, a greater understanding of the biology of C. albicans is needed. In these studies, we are focused on the fundamental biological process of endocytosis, of which little is directly known in C. albicans. In addition to studying the function of a key gene in this process, we are examining the role of endocytosis in the virulence-related processes of filamentation, biofilm formation, and tissue invasion. These studies will provide greater insight into the role of endocytosis in causing invasive fungal infections. |
Databáze: | OpenAIRE |
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