Boudreau Marc A, Fishovitz Jennifer, Llarrull Leticia I, Xiao Qiaobin, Mobashery Shahriar
Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
ACS Infect Dis. 2015 Oct 9;1(10):454-9. doi: 10.1021/acsinfecdis.5b00086. Epub 2015 Aug 24.
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.
耐甲氧西林金黄色葡萄球菌（MRSA）是一种重要的人类病原体，它已经进化出一种对β-内酰胺抗生素的诱导抗性机制。我们在此报告，完整膜蛋白BlaR1，即β-内酰胺传感器/信号转导蛋白，在暴露于β-内酰胺抗生素时会发生磷酸化。这一事件对于抗生素抗性诱导的开始至关重要。此外，我们证明，在我们设计的合成蛋白激酶抑制剂存在的情况下，BlaR1磷酸化和抗生素抗性表型都会逆转，恢复该生物体对青霉素的敏感性，使其在治疗这些顽固细菌时从过时状态中复活。
