Language
English
Publication Date
10-11-2025
Journal
bioRxiv
DOI
10.1101/2025.10.02.680127
PMID
41256586
PMCID
PMC12622048
PubMedCentral® Posted Date
10-11-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Antimicrobial resistance (AMR) is an existential threat to modern healthcare; one fueled by selection pressure provided by the use of broad-spectrum antibiotics in medicine and agriculture. As these antibiotics rely on a small set of chemical scaffolds and affect an even smaller number of biological targets, emergent AMR genes can spread through microbiomes to simultaneously inactivate multiple classes and generations of drugs. Long-overlooked for their perceived clinical limitations, antibacterial natural products with taxa-specific activities now present an underexplored source of design principles for precision antibiotics that can selectively eliminate individual microbes and limit community-wide incentives for AMR. Here, we present our re-investigation of one such taxa-specific antibacterial natural product, imacidin, a forgotten inhibitor of cell wall biosynthesis. We show that imacidin is the first natural product inhibitor of the peptidoglycan lipid II flippase MurJ, representing a larger, nascent class of taxa-specific cyclic lipopeptides that offer new leads for precision antibiotics.
Published Open-Access
yes
Recommended Citation
Barrois, Elizabeth B; Costa-Martini, Jonas H; Thoma, Lina; et al., "Cyclic Lipopeptide Natural Products As Taxa-Specific Antibacterial Inhibitors of the Lipid II Flippase" (2025). Faculty, Staff and Students Publications. 8354.
https://digitalcommons.library.tmc.edu/baylor_docs/8354