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

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-lac...

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Published inACS infectious diseases Vol. 1; no. 10; pp. 454 - 459
Main Authors Boudreau, Marc A, Fishovitz, Jennifer, Llarrull, Leticia I, Xiao, Qiaobin, Mobashery, Shahriar
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 09.10.2015
Subjects
Stk1
kinase inhibitor
BlaR1
phosphorylation
MRSA
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Summary: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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ISSN:2373-8227
2373-8227
DOI:10.1021/acsinfecdis.5b00086