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

ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA), an important human pathogen, has evolved an inducible mechanism for resistance to ?-lactam antibiotics. We report herein that the integral membrane protein BlaR1, the ?-lactam sensor/signal transducer protein, is phosphorylated on exposure to ?-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.

SUBMITTER: Boudreau MA

PROVIDER: S-EPMC5022795 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Boudreau Marc A MA Fishovitz Jennifer J Llarrull Leticia I LI Xiao Qiaobin Q Mobashery Shahriar S

ACS infectious diseases 20150824 10

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 rev ...[more]

PMID: 27623311

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