# Novel linear lipopeptide paenipeptins sensitize multidrug-resistant Gram-negative pathogens to antibiotics

> **NIH NIH R21** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $190,000

## Abstract

PROJECT SUMMARY
The Infectious Diseases Society of America recently identified a list of antibiotic-resistant pathogens that can
escape the effect of most antimicrobial agents. These problematic pathogens include Enterococcus faecium,
Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and
Enterobacter spp., which are collectively abbreviated as ESKAPE. Therefore, there is an urgent need to
develop effective antibiotics to keep up with antibiotic resistance.
Paenipeptins are novel synthetic linear lipopeptides, which are made of 9 amino acid residues and a fatty acyl
group at the N-terminus. They showed highly potent activity in combination with clarithromycin against Gram-
negative pathogens in vitro. The overall goal of this project is to develop novel linear lipopeptide antibiotic
potentiators, which can be co-administered with FDA-approved antibiotics, to expand their antimicrobial
spectrum and enhance the antibiotic activity for the treatment of infections associated with polymyxin-resistant
and carbapenem-resistant pathogens. To achieve this goal, the following two aims are set.
Aim 1: Evaluate the synergistic effect between paenipeptin analogues and clarithromycin in vitro against a
large number of carbapenem-resistant clinical isolates and investigate the mechanism of synergism.
Aim 2: Develop antimicrobial-loaded hydrogels for localized delivery of paenipeptin-clarithromycin mixture for
topical treatment of wound infections.

## Key facts

- **NIH application ID:** 9936116
- **Project number:** 5R21AI146693-02
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** En Huang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,000
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936116

## Citation

> US National Institutes of Health, RePORTER application 9936116, Novel linear lipopeptide paenipeptins sensitize multidrug-resistant Gram-negative pathogens to antibiotics (5R21AI146693-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9936116. Licensed CC0.

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