# Biofilm Induced Extracellular Vesicle Pathogenesis

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $378,741

## Abstract

PROJECT SUMMARY: One of Candida albicans' most impressive virulence attributes is the ability to
propagate as a biofilm when attached to a medical device, such as a venous catheter. This critical factor alone
is responsible for the majority of persistent and disseminated infections. As conventional antimicrobials are
ineffective for treatment of these life-threatening infections, further understanding of the biofilm lifestyle,
including how the cells survive drug therapy and disperse to distant organs is desperately needed. The
microbe-derived extracellular matrix, a distinguishing feature of biofilms, has been linked to several roles in
biofilm pathogenesis. The proposed investigation capitalizes on our progress during the last funding period that
identified the role of a polysaccharide mannan-glucan complex for biofilm resistance and dispersion. We were
surprised to find the maturation process occurred in the extracellular space. However, it was unclear how these
matrix materials were delivered and assembled. Our preliminary study of the genesis and role of a lipid matrix
component provides compelling evidence for vesicle cargo delivery of matrix components critical for drug
resistance. This process also appears to regulate biofilm cell dispersion. Our excitement for future investigation
of the function of vesicle cargo in biofilm pathogenesis is based upon four unexpected observations. First, we
identified vesicles in the extracellular matrix, and these biofilm-derived vesicles carry a distinct cargo that is
different from vesicles of free-living (planktonic) cells. Second, we identified vesicle-defective mutants affecting
the ESCRT complex; these mutants are impaired in accumulation of matrix and display phenotypes of other
matrix-defective mutants (biofilm drug susceptibility and reduced cell dispersion). Third, the cargo of these
vesicle mutants differed from vesicles produced by WT strains. Fourth, several cargo mutants display biofilm
resistance and dispersion defects, and are rescued by addition of wild-type extracellular vesicles. Our major
objectives now are to define the vesicle cargo responsible for the matrix drug resistance, to define the vesicle
cargo responsible for cell dispersion, and to discern the genetic pathways that orchestrate this novel process
during biofilm pathogenesis.

## Key facts

- **NIH application ID:** 10176360
- **Project number:** 5R01AI073289-14
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** David R Andes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,741
- **Award type:** 5
- **Project period:** 2008-06-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176360

## Citation

> US National Institutes of Health, RePORTER application 10176360, Biofilm Induced Extracellular Vesicle Pathogenesis (5R01AI073289-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10176360. Licensed CC0.

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