Structure-activity studies of the bacteriocin bactofencin A and its interaction with the bacterial membrane

Authors: Biron, ÉricBédard, FrançoisFliss, Ismaïl
Abstract: The antimicrobial peptide bactofencin A is an unmodified non-pediocin-like bacteriocin that inhibits several clinically relevant pathogens, including Listeria monocytogenes and Staphylococcus aureus. Here we report the synthesis and structure–activity relationship studies of bactofencin A and novel analogues thereof. Synthetic bactofencin A was a potent inhibitor of L. monocytogenes (MIC = 8.0 μM) and S. aureus (MIC = 4.0 μM), similar to the bacteriocin produced naturally by Lactobacillus salivarius. Of particular interest is the fact that linear analogues lacking the disulfide bond found in bactofencin A were as potent and also active against several strains of methicillin-resistant S. aureus (MRSA) and one strain of vancomycin-resistant S. aureus (VRSA). Supported by the structure–activity relationship study, investigation of the interaction of bactofencin A with bacterial membrane by molecular dynamics simulations showed the importance of the positively charged N-terminal tail for peptide–membrane interaction. These results suggest that the C-terminal macrocycle is involved in target protein binding and bacterial growth inhibition.
Document Type: Article de recherche
Issue Date: 12 December 2018
Open Access Date: 12 December 2019
Document version: AM
Permalink: http://hdl.handle.net/20.500.11794/34237
This document was published in: ACS Infectious Diseases
http://dx.doi.org/10.1021/acsinfecdis.8b00204
American Chemical Society
Alternative version: 10.1021/acsinfecdis.8b00204
Collection:Articles publiés dans des revues avec comité de lecture

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