Mechanism of reduced vancomycin susceptibility conferred by walK mutation in community-acquired methicillin-resistant Staphylococcus aureus strain MW2

Jinfeng Hu; Xu Zhang; Xiaoyu Liu; Chuan Chen; Baolin Sun

doi:10.1128/AAC.04290-14

Mechanism of reduced vancomycin susceptibility conferred by walK mutation in community-acquired methicillin-resistant Staphylococcus aureus strain MW2

Antimicrob Agents Chemother. 2015 Feb;59(2):1352-5. doi: 10.1128/AAC.04290-14. Epub 2014 Dec 1.

Authors

Jinfeng Hu¹, Xu Zhang¹, Xiaoyu Liu¹, Chuan Chen¹, Baolin Sun²

Affiliations

¹ Department of Microbiology and Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China.
² Department of Microbiology and Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, China [email protected].

Abstract

Point mutations with unclear molecular mechanisms are often associated with vancomycin resistance in Staphylococcus aureus. Here, we observed that the walK (G223D) mutation caused decreased expression of genes associated with cell wall metabolism, decreased autolytic activity, thickened cell walls, and reduced vancomycin susceptibility. A phosphorylation assay showed that WalK (G223D) exhibited reduced autophosphorylation, which led to reduced phosphorylation of WalR. An electrophoretic mobility shift assay indicated that WalK (G223D)-phosphorylated WalR had a reduced capacity to bind to the atlA promoter.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Methicillin-Resistant Staphylococcus aureus / drug effects*
Mutation
Phosphorylation
Promoter Regions, Genetic / genetics
Staphylococcus aureus / drug effects
Vancomycin / pharmacology*

Substances

Vancomycin