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.
journal_name
Proc Natl Acad Sci U S Aauthors
Cochrane SA,Findlay B,Bakhtiary A,Acedo JZ,Rodriguez-Lopez EM,Mercier P,Vederas JCdoi
10.1073/pnas.1608623113subject
Has Abstractpub_date
2016-10-11 00:00:00pages
11561-11566issue
41eissn
0027-8424issn
1091-6490pii
1608623113journal_volume
113pub_type
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