Antimicrobial Lipopeptide Tridecaptin A1 Selectively Binds to Gram-negative Lipid II

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2016 Oct 1

PMID 27688760

Citations 60

Authors

Stephen A Cochrane

Brandon Findlay

Alireza Bakhtiary

Jeella Z Acedo

Eva M Rodriguez-Lopez

Pascal Mercier

John C Vederas

Affiliations

Soon will be listed here.

Abstract

Tridecaptin A (TriA) is a nonribosomal lipopeptide with selective antimicrobial activity against Gram-negative bacteria. Here we show that TriA exerts its bactericidal effect by binding to the bacterial cell-wall precursor lipid II on the inner membrane, disrupting the proton motive force. Biochemical and biophysical assays show that binding to the Gram-negative variant of lipid II is required for membrane disruption and that only the proton gradient is dispersed. The NMR solution structure of TriA in dodecylphosphocholine micelles with lipid II has been determined, and molecular modeling was used to provide a structural model of the TriA-lipid II complex. These results suggest that TriA kills Gram-negative bacteria by a mechanism of action using a lipid-II-binding motif.

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