# Investigation of capsule interactions that promote antimicrobial peptide activity

> **NIH NIH R21** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $194,615

## Abstract

Project Summary.
The extracellular polysaccharide capsule of Klebsiella pneumoniae resists penetration by antimicrobials and
protects the bacteria from the innate immune system. While capsule inhibits most host defense peptides and
polymyxin antibiotics, a few amphipathic antimicrobial peptides have been identified that retain activity against
capsulated K. pneumoniae. However, it is not known what enables some peptides to avoid sequestration by K.
pneumoniae capsule while it effectively neutralizes most others. We have uncovered a mechanism that allows
synthetic antimicrobial peptides to overcome capsule inhibition. Specific amino acid changes in inactive
sequences enable peptides to bind, aggregate, and disrupt capsule layers, leaving K. peumoniae vulnerable to
their membrane attack. Through this proposal we will 1) explore this new mechanism in innate immune host
defense peptides that kill capsulated K. pneumoniae, and 2) characterize amino acid sequence and positional
variations that promote activity towards capsulated bacteria. Our results will provide important insight into
immune evasion by K. pneumoniae and other capsulated bacteria, and identify mechanistic principles will aid
the development new therapeutic approaches to overcome the capsule barrier.

## Key facts

- **NIH application ID:** 10193371
- **Project number:** 1R21AI159203-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Bryan William Davies
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,615
- **Award type:** 1
- **Project period:** 2021-03-19 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10193371

## Citation

> US National Institutes of Health, RePORTER application 10193371, Investigation of capsule interactions that promote antimicrobial peptide activity (1R21AI159203-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10193371. Licensed CC0.

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