Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus Aureus and Its Abrogation by Small Molecules

Overview

Journal ACS Infect Dis

Specialties Infectious Diseases
Microbiology
Pharmacology

Date 2016 Sep 14

PMID 27623311

Citations 20

Authors

Marc A Boudreau

Jennifer Fishovitz

Leticia I Llarrull

Qiaobin Xiao

Shahriar Mobashery

Affiliations

Soon will be listed here.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), an important human pathogen, has evolved an inducible mechanism for resistance to β-lactam antibiotics. We report herein that the integral membrane protein BlaR1, the β-lactam sensor/signal transducer protein, is phosphorylated on exposure to β-lactam antibiotics. This event is critical to the onset of the induction of antibiotic resistance. Furthermore, we document that BlaR1 phosphorylation and the antibiotic-resistance phenotype are both reversed in the presence of synthetic protein kinase inhibitors of our design, restoring susceptibility of the organism to a penicillin, resurrecting it from obsolescence in treatment of these intransigent bacteria.

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