# Development of a broad spectrum teixobactin-lipopeptide hybrid for the treatment of lung infections caused by pan-drug resistant ‘superbugs’

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $732,598

## Abstract

ABSTRACT
The goal of this project is to develop a broad-spectrum dry powder inhalation teixobactin-lipopeptide
hybrid aimed at preventing and treating lung infections caused by bacterial `superbugs'. The successful
use of any antibiotic is compromised by the potential development of resistance to that compound from the
time it is first used. The world is facing an enormous and growing threat from the emergence of pan-drug
resistant (PDR) bacteria that are resistant to all available antibiotics. New antibiotics with 1) novel mechanisms
of action and 2) against which bacteria cannot easily develop resistance are urgently needed to treat lung
infections caused by the PDR Gram-negative pathogens like Pseudomonas aeruginosa, Acinetobacter
baumannii and Klebsiella pneumoniae and Gram-positive strains of methicillin-resistant Staphylococcus aureus
(MRSA) and Streptococcus pneumoniae. Teixobactin is a recently discovered new antibiotic that possesses a
novel mechanism of action (MOA), albeit, a narrow spectrum of activity against Gram-positive bacteria. The
most notable property of teixobactin is that it is the first and only antibiotic that bacteria cannot easily develop
resistance against. We have developed novel teixobactin-lipopeptide hybrids that are superior to native
teixobactin as they retain this key anti-resistance property and in addition have a broader-spectrum,
with potent activity against PDR Gram-negatives, as well as PDR Gram-positives. Our preliminary data
show that our teixobactin-lipopeptide hybrids delivered as a dry powder inhalation have significantly improved
efficacy for the treatment of lung infections by virtue of their unique MOA, no detectable resistance, high local
exposure in the lungs with low systemic exposure and low toxicity. Importantly, the hybrids displayed superior
in vivo efficacy compared to treatment with the combination of the individual compounds or each compound
per se. This is a significant development in the field as the teixobactin-lipopeptide hybrid represents
the first-in class broad-spectrum `resistance-proof' dry powder inhalation antibiotic for the treatment of
PDR bacterial lung infections. Our internationally recognized track records in antibiotic discovery,
pharmacology, anti-infective dry powder formulation, pharmacokinetics/pharmacodynamics and state-of-the-art
facilities for antimicrobial development provide extremely strong support for this project. The proposal will
employ a purpose designed funneling approach to identify a lead candidate (plus one back-up) that is active
against PDR Gram-negative strains of P. aeruginosa, A. baumannii and K. pneumoniae and Gram-positive
strains of MRSA and S. pneumoniae for preclinical development and IND-enabling studies.

## Key facts

- **NIH application ID:** 10832091
- **Project number:** 5R01AI170889-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Sara Elizabeth Maloney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $732,598
- **Award type:** 5
- **Project period:** 2022-06-21 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832091

## Citation

> US National Institutes of Health, RePORTER application 10832091, Development of a broad spectrum teixobactin-lipopeptide hybrid for the treatment of lung infections caused by pan-drug resistant ‘superbugs’ (5R01AI170889-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10832091. Licensed CC0.

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