# C. albicans invasion and proliferation during oral infection

> **NIH NIH R01** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 2020 · $584,377

## Abstract

Abstract
 Oropharyngeal candidiasis (OPC) causes significant morbidity in a large, diverse population, especially
patients who are immunocompromised due to AIDS, neutropenia, diabetes mellitus, or the use of steroids. In
fact, it is estimated that nearly 10 million cases of HIV/AIDS-associated OPC occur annually, and nearly a fifth
of these individuals have esophageal involvement. Azole antifungal agents are the current mainstay of therapy
for OPC. However, because of the emergence of azole resistance, it is critical to develop novel strategies to
prevent and treat OPC.
 Our studies have focused on the hypothesis that C. albicans genes that promote adherence to and invasion
of epithelial cells are critical for the organism to cause OPC. This hypothesis is based on the fact that invasion
of the superficial epithelium occurs during OPC, and that biopsy specimens from OPC patients reveal organisms
within oral epithelial cells. Adherence/invasion functions are carried out by cell surface proteins that interact with
cognate receptors on host cells. These interactions enable the organism to invade oral epithelial cells and avoid
being killed by phagocytes. Our data indicate that there are two adherence/invasion pathways that function in
OPC. Pathway I includes the C. albicans surface proteins Als3 and Ssa1, which interact with the epithelial cell
surface proteins epidermal growth factor receptor (EGFR) and HER2. Pathway II is newly described in our
preliminary results. Pathway II includes the C. albicans surface protein Hyr1, which binds to the c-Met receptor
tyrosine kinase on both oral epithelial cells and neutrophils. Our overall premise is that both Pathway I and
Pathway II promote endocytosis of C. albicans by oral epithelial cells through E-cadherin. Pathway II also
functions when C. albicans interacts with neutrophils to inhibit neutrophil killing.
 The objectives of the proposed studies are to test Pathway II function and its mechanistic basis, and to
define the relationships between Pathway I and Pathway II. We will 1) determine the role of the Hyr1-c-Met
interaction in inhibition of neutrophil fungicidal activity and epithelial cell invasion; 2) define the functional
relationships among Hyr1 and the cell surface invasins Als3 and Ssa1 in vitro and in vivo; and 3) define additional
Pathway I and II genes that function during OPC. The results from this research will provide new insight into the
mechanisms by which C. albicans invades oral epithelial cells and down-regulates neutrophil fungicidal
mechanisms. Not only will these data provide a deeper understanding of the pathogenesis of OPC, but they
also hold promise to identify new potential drug and vaccine targets.

## Key facts

- **NIH application ID:** 9894647
- **Project number:** 5R01DE026600-04
- **Recipient organization:** LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
- **Principal Investigator:** Scott G Filler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $584,377
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894647

## Citation

> US National Institutes of Health, RePORTER application 9894647, C. albicans invasion and proliferation during oral infection (5R01DE026600-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9894647. Licensed CC0.

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