The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II)

Zarkan, Ashraf, Macklyne, Heather-Rose, Truman, Andrew W, Hesketh, Andrew R and Hong, Hee-Jeon (2016) The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II). Scientific Reports, 6. ISSN 2045-2322

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Abstract

Vancomycin is a front-line antibiotic used for the treatment of nosocomial infections, particularly those caused by methicillin-resistant Staphylococcus aureus. Despite its clinical importance the global effects of vancomycin exposure on bacterial physiology are poorly understood. In a previous transcriptomic analysis we identified a number of Zur regulon genes which were highly but transiently up-regulated by vancomycin in Streptomyces coelicolor. Here, we show that vancomycin also induces similar zinc homeostasis systems in a range of other bacteria and demonstrate that vancomycin binds to Zn(II) in vitro. This implies that vancomycin treatment sequesters zinc from bacterial cells thereby triggering a Zur-dependent zinc starvation response. The Kd value of the binding between vancomycin and Zn(II) was calculated using a novel fluorometric assay, and NMR was used to identify the binding site. These findings highlight a new biologically relevant aspect of the chemical property of vancomycin as a zinc chelator.

Item Type: Article
Keywords: microbiology, antibiotic resistance
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Heather-Rose Macklyne
Date Deposited: 25 Jan 2016 08:31
Last Modified: 13 Mar 2017 02:08
URI: http://sro.sussex.ac.uk/id/eprint/59412

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