# Refining our understanding of antimicrobial peptide mediated disruption of the Klebsiella pneumoniae capsule

> **NIH NIH K99** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $108,195

## Abstract

Project Summary
Multi-drug resistant Klebsiella pneumoniae bacterial infections are a major threat to human health as mortality
rates are steadily on the rise. One of the defining characteristics of K. pneumoniae is a robust capsule that aids
in resistance to the human complement system, host antimicrobial peptides, and last resort therapeutic
polymyxins. However, there have not been significant efforts to identify the attributes that allow active peptides
to bypass the capsule of K. pneumoniae. I have previously discovered a novel mechanism of peptide
disruption of the capsule barrier of K. pneumoniae. I hypothesize there are amino acid residues that change
the physiochemical attributes and allow for penetration through the capsule. During the K99 phase of this
proposal I will: 1) Define how host defense peptides fit into the novel mechanism of capsule disruption; and 2)
Identify broader set of physiochemical characteristics that allow for disruption of the K. pneumoniae capsule.
The objective of these aims is to determine how well studied host defense peptides fit into the mechanism of
capsule disruption using biochemical and biophysical experiments and determine the physiochemical attributes
that allow for peptide aggregation and disruption of K. pneumoniae capsule. The R00 phase will build on the
K99 phase, to identify the structural components of bacterial capsule that is aggregating with peptides and
reveal the implications of therapeutic capsule removal on the infection process of K. pneumoniae using
peptides discovered in the K99 phase. The K99/R00 award will allow me to utilize the extensive resources
available at the University of Texas at Austin while working with my mentor team to ensure successful
transition to an independent research position. The results of the studies completed in this award will provide a
greater understanding of peptide disruption of capsule and how this changes the infection process of K.
pneumoniae.

## Key facts

- **NIH application ID:** 10283340
- **Project number:** 1K99AI163295-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Renee Fleeman
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $108,195
- **Award type:** 1
- **Project period:** 2021-08-24 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283340

## Citation

> US National Institutes of Health, RePORTER application 10283340, Refining our understanding of antimicrobial peptide mediated disruption of the Klebsiella pneumoniae capsule (1K99AI163295-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10283340. Licensed CC0.

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