# Endocytosis in Candida filamentation, biofilm formation and virulence

> **NIH VA I01** · WHITE RIVER JUNCTION VA MEDICAL CENTER · 2024 · —

## Abstract

The fungus Candida albicans is the 4th most common cause of hospital-acquired bloodstream infections
(BSI), and is a major cause of intravenous catheter-associated infections, urinary infections, skin and mucosal
infections, and invasive disease in our veteran patient population. Despite advancements in medical care, the
high mortality rate due to invasive Candida infections is no better than two decades ago. Thus, our ability to
prevent, diagnose, and treat invasive Candida infections is still in need of great improvement. Although C.
albicans is a normal human colonizer, it has the ability to cause disease through various specialized attributes.
These virulence-associated factors include secretion of degradative enzymes that assist in tissue invasion,
formation of elongated hyphal structures in a process termed filamentation, and establishment of complex
structures called biofilms, which protect this fungus from antimicrobial drugs and host immune defenses.
 In previous studies, we examined the role of the pre-vacuolar secretory pathway in the secretion of
virulence-associated proteins and biofilm formation in C. albicans, regulated by the vacuolar protein secretion
genes VPS1, VPS4, and PEP12. We demonstrated that this pre-vacuolar secretory pathway contributes to
secretion of a key degradative enzyme, secreted aspartyl protease, and is involved in aspects of filamentation,
biofilm formation, and virulence. For example, we discovered that the C. albicans pep12 null mutant formed a
biofilm that dramatically fragmented with minimal disturbance, and was defective in virulence in vivo.
Expanding upon these studies, we next studied the late stages of secretion by examining key final steps in
exocytosis regulated by the exocyst protein complex. In this work, we demonstrated that the exocyst-related
SNARE proteins Sso2p and Sec9p were essential for viability in C. albicans, and were required for the
secretion of aspartyl proteases and lipases, and hyphal formation. In contrast, several major components of
the exocyst complex, including Exo70p and Exo84p, and the regulatory protein Sro77p did not appear to be
required for filamentation.
 Next, we have begun studies of another essential component of the secretory pathway, that is, endocytosis
and the endocytic pathway. This highly regulated, sequential pathway is involved in intake of extracellular
materials and recycling of plasma membrane proteins and other components of the secretory pathway. Our
main objective is to determine the role of endocytosis in secretion, filamentation, biofilm formation, and
virulence. Further, we will study the specific contributions of endocytosis to filamentation from a mechanistic
standpoint. This project will therefore examine the key hypotheses that: (i) specific genes in key steps of
endocytosis are required for filamentation and biofilm formation, (ii) mutations in endocytosis pathway genes at
key steps will result in attenuated virulence in vitro and in vivo, and ...

## Key facts

- **NIH application ID:** 10884149
- **Project number:** 5I01BX004128-07
- **Recipient organization:** WHITE RIVER JUNCTION VA MEDICAL CENTER
- **Principal Investigator:** SAMUEL AUSTIN LEE
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884149

## Citation

> US National Institutes of Health, RePORTER application 10884149, Endocytosis in Candida filamentation, biofilm formation and virulence (5I01BX004128-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10884149. Licensed CC0.

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