MRSA Research Today is a free monthly online journal that collates and summarizes the latest research about MRSA, including details on methicillin-resistant staphylococcus aureus, hospitals, infection, antibiotic resistance, superbugs. | ||||||||
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Identification and phenotypic characterization of a {beta}-lactam-dependent, methicillin-resistant Staphylococcus aureus (MRSA).Goldstein F, Perutka J, Cuirolo A, Plata K, Faccone D, Morris J, Sournia A, Kitzis MD, Ly A, Archer G, Rosato AE Division of Infectious Diseases, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298; Foundation Hospital Saint Joseph, 185 rue Raymond Losserand, 75014, Paris, France; Department of Molecular Biology, University of Gdansk, Kladki 24, 84-822 Gdansk, Poland. Methicillin-resistance in S.aureus is primarily mediated by the acquired penicillin-binding protein (PBP2a) which is encoded by mecA. PBP2a acts together with native PBP2 to mediate oxacillin resistance by contributing complementary transpeptidase and transglycosylase activities, respectively. In this study, we have investigated a phenotype of beta-lactam dependence in a clinical MRSA strain (SA2884D) obtained by in-vitro selection with ceftobiprole. SA28884D, which grew very poorly in blood agar, required the presence of the beta-lactam antibiotics to grow. Based in this observation, we hypothesized that a gene or genes essential for growth were dependent on oxacillin induction. Identification and analysis of genes regulated by oxacillin was performed by both Real-Time RT-PCR and Spotted Microarray analysis. We found mecA constitutively expressed in SA2884D which resulted from perturbations in the two systems involved in its regulation, i.e., MecI/MecR1 (SCCmec Type I) and BlaI/BlaR1 (non-functional penicillinase operon). PBP2 appeared poorly induced by oxacillin in SA2884D. Further analysis of the PBP2 two-component VraSR regulatory system showed that it was non-functional accounting for the lack of response to oxacillin. Together, these results support the notion that a limited PBP2 availability may have led SA2884D to become dependent on oxacillin-mediated mecA induction as a required survival mechanism. Published 1 May 2007 in Antimicrob Agents Chemother.
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