# Inhibition of Candida virulence and biofilm formation by a bacterial peptide

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $545,991

## Abstract

PROJECT SUMMARY/ABSTRACT
The medical condition oropharyngeal candidiasis (OPC) is a major source of oral morbidity in patient groups
including the immunosuppressed (cancer and AIDS patients) and those taking broad-spectrum antibiotics. We
recently identified a peptide produced by Enterococcus faecalis that inhibits the hyphal morphogenesis and
biofilm formation of the primary causative agent of OPC, Candida albicans. The research proposed in this ap-
plication seeks to understand how the mature form of this peptide, EntV, is generated, how it targets C. albi-
cans hyphal morphogenesis, and the extent to which it protects against OPC, thereby filling a critical gap in our
knowledge and providing new avenues for the development of therapeutics. The long-term goal of this re-
search is to develop novel strategies for treating and preventing oropharyngeal candidiasis. The objective of
this application is to determine the generation, mode of action and therapeutic potential of EntV. The central
hypothesis is that secreted and processed EntV acts on signaling pathway(s) that controls hyphal development
in C. albicans resulting in protection from candidiasis. The rationale for this research is that identification of the
mechanism by which EntV inhibits the formation of the invasive form of C. albicans will lead to new treatment
strategies. By pursing three aims, the objective of this application will be attained. Aim #1 will elucidate how the
active form of EntV is generated. Using both genetic and biochemical approaches, we will test the hypothesis
that the proteases GelE and/or SprE are required for cleavage, and disulfide bond formation is catalyzed by a
DsbA homolog. In Aim #2, the genes/pathways of C. albicans that are targeted by E. faecalis to inhibit hyphal
morphogenesis will be determined using cell biological and genetic approaches. Based on preliminary data,
the working hypothesis is that EntV interacts directly with one of several known discrete subdomains on the C.
albicans cell surface to disrupt cell-cell and cell-substrate adherence, both of which are essential for biofilm
formation. The efficacy of EntV and related peptides in protecting against C. albicans infection will be tested in
Aim #3. Tissue culture cells (macrophages and oral epithelial cells) and mouse models of OPC and gastroin-
testinal colonization will be utilized. We postulate that EntV will protect against C. albicans infection and can-
didiasis in the nanomolar range. The significance of this contribution will be the knowledge of how a bacterial
peptide inhibits C. albicans hyphal morphogenesis, potentially opening new avenues for therapeutic design.
Targeting hyphal morphogenesis as an area for the possible development of novel therapeutics is innovative,
as current antifungals are directed against the integrity or growth of the cell envelope. Additional benefits of this
research include new knowledge in the fields of bacterial peptide generation, fungal morphotype swi...

## Key facts

- **NIH application ID:** 10167681
- **Project number:** 5R01DE027608-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Danielle A Garsin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $545,991
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167681

## Citation

> US National Institutes of Health, RePORTER application 10167681, Inhibition of Candida virulence and biofilm formation by a bacterial peptide (5R01DE027608-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10167681. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*