# Identification and development of antimicrobial peptoids effective against cross-kingdom biofilms

> **NIH NIH R03** · MIDDLE TENNESSEE STATE UNIVERSITY · 2020 · $65,400

## Abstract

Identification and development of antimicrobial peptoids effective against cross-kingdom biofilms
Project Summary
 The purposed work focuses on identifying antimicrobial compounds targeting cross-kingdom
biofilms generated by Candida albicans and bacteria through high-throughput screening of a one bead one
compound combinatorial library. C. albicans is the third most common source of hospital acquired
infections and the primary source of hospital acquired fungal infections, with high rates of morbidity and
mortality. C. albicans often forms cross-kingdom polymicrobial biofilms with other infectious microbes.
These cross-kingdom interactions can be synergistic and result in unique quorum-sensing that causes
increased drug resistance. Antimicrobial drugs that treat both the fungal and the bacterial infections within
a complex, synergistic biofilm would provide a valuable therapeutic option to those dealing with deadly
hospital acquired cross-kingdom biofilm infections. Once such option could be antimicrobial peptoids.
Peptoids are a useful class of peptidomimetics due to ease of synthesis, increased bioavailability, and
decreased protease recognition compared with peptides. Our lab and others have demonstrated the
antimicrobial efficacy of peptoids against both bacterial and fungal pathogens. Additionally, reports
demonstrate modest efficacy of antimicrobial peptoids against both monospecial and cross-kingdom
biofilms. However, the low throughput nature of these antimicrobial peptoid reports limits the compound
chemical diversity and biofilm species variety they can explore. The overall goal of this proposal is to
identify antimicrobial peptoids effective against C. albicans/bacterial cross-kingdom biofilms through the
adaption and use of our previously developed PLAD high-throughput assay.
 Specific work proposed here will include the synthesis of several combinatorial peptoid libraries
and screening of these libraries using our high-throughput Peptoid Library Agar Diffusion (PLAD) assay
with subsequent testing to evaluate antibiofilm activity. Additionally, we will also adapt our PLAD assay
to screen peptoid libraries against mature, established biofilms to directly generate peptoids with
antibiofilm activity. Antibiofilm compounds rapidly identified using these techniques will be resynthesized
and their broad antibiofilm activity and preliminary cytotoxicity evaluated using traditional methods to
generate lead compounds. Successful completion of this work will result in antibiofilm peptoids that can
be further developed into therapeutic options for individuals dealing with deadly cross-kingdom biofilm
infections on wounds, prosthetics, and other surfaces.

## Key facts

- **NIH application ID:** 9976086
- **Project number:** 1R03AI146393-01A1
- **Recipient organization:** MIDDLE TENNESSEE STATE UNIVERSITY
- **Principal Investigator:** Kevin Bicker
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,400
- **Award type:** 1
- **Project period:** 2020-02-18 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976086

## Citation

> US National Institutes of Health, RePORTER application 9976086, Identification and development of antimicrobial peptoids effective against cross-kingdom biofilms (1R03AI146393-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9976086. Licensed CC0.

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