Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection

Moule, Madeleine G.; Benjamin, Aaron B.; Burger, Melanie L.; Herlan, Claudine; Lebedev, Maxim; Lin, Jennifer S.; Koster, Kent J.; Wavare, Neha; Adams, Leslie G.; Bräse, Stefan; Munoz-Medina, Ricardo; Cannon, Carolyn L.; Barron, Annelise E.; Cirillo, Jeffrey D.

doi:10.1038/s42003-024-06725-1

Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection

Journal Article · Thu Aug 22 00:00:00 EDT 2024 · Communications Biology

DOI:https://doi.org/10.1038/s42003-024-06725-1· OSTI ID:2469716

^[1]; Benjamin, Aaron B. ^[2]; Burger, Melanie L. ^[3]; Herlan, Claudine ^[4]; Lebedev, Maxim ^[2]; Lin, Jennifer S. ^[5]; Koster, Kent J. ^[2]; Wavare, Neha ^[2]; ^[2]; Bräse, Stefan ^[4]; Munoz-Medina, Ricardo ^[2]; Cannon, Carolyn L. ^[2]; ^[5]; ^[2]

Texas A&M School of Medicine, Bryan, TX (United States); Univ. of Edinburgh, Scotland (United Kingdom)
Texas A&M School of Medicine, Bryan, TX (United States)
Univ. of Edinburgh, Scotland (United Kingdom)
Karlsruhe Inst. of Technology (KIT) (Germany)
Stanford Univ., CA (United States)

The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30–60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Molecular Foundry

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2469716

Journal Information:: Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 7; ISSN 2399-3642

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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