Antimicrobial lipopeptide tridecaptin A1 selectively binds to Gram-negative lipid II.

Abstract:

:Tridecaptin A1 (TriA1) is a nonribosomal lipopeptide with selective antimicrobial activity against Gram-negative bacteria. Here we show that TriA1 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 TriA1 in dodecylphosphocholine micelles with lipid II has been determined, and molecular modeling was used to provide a structural model of the TriA1-lipid II complex. These results suggest that TriA1 kills Gram-negative bacteria by a mechanism of action using a lipid-II-binding motif.

authors

Cochrane SA,Findlay B,Bakhtiary A,Acedo JZ,Rodriguez-Lopez EM,Mercier P,Vederas JC

doi

10.1073/pnas.1608623113

subject

Has Abstract

pub_date

2016-10-11 00:00:00

pages

11561-11566

issue

41

eissn

0027-8424

issn

1091-6490

pii

1608623113

journal_volume

113

pub_type

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