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

Scientific Reports
Ashraf ZarkanHee-Jeon Hong

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.

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Citations

Aug 2, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Giorgio FacchettiIsabella Rimoldi
Apr 19, 2020·Applied Microbiology and Biotechnology·Qian YeYishan Zheng

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Methods Mentioned

BETA
affinity column chromatography
NMR
PCR

Software Mentioned

7300 system SDS
TopSpin
DynaFit

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