Abstract
Background. Ceftaroline is one of the first cephalosporins with activity against methicillin-resistant Staphylococcus aureus (MRSA), it effectively binds to and inhibits penicillin-binding protein 2a (PBP2a). However, isolates with decreased susceptibility to ceftaroline were reported before the commercial release of the antibiotic.
 The aim of this study was to provide an overview of the proteome changes occurring in MRSA isolates resistant to ceftaroline in response to sub-inhibitory concentrations of cell-wall active antibiotics.
 Materials and methods. Ceftaroline-resistant mutants were generated from two MRSA SA0077 and SA0422 isolates belonging to ST8-t008-SCCmec IV genetic lineage (sequence type 8, spa type t008, staphylococcal chromosomal cassette mec type IV) and one MRSA isolate SA0085 belonging to ST239-t631-SCCmec III genetic lineage (sequence type 239, spa type t631, staphylococcal chromosomal cassette mec type III). Proteome response of parental and mutant strains to sub-inhibitory concentration of beta-lactams and vancomycin was analyzed.
 Results. The protein patterns revealed significant increase of 30 кDа band in mutant strains under induction by meropenem, no changes were observed in parental strains or under induction with other antibiotics. According to MS analysis, three proteins represented the band of the mutant strain in absence of meropenem induction. However, under meropenem induction additional protein was detected (BlaZ).
 Conclusion. The cross talk between two systems with overlapping functions involved in transcription control of PBP2a and BlaZ ensure ceftaroline resistant phenotype.
Highlights
CC Устойчивость к цефтаролину — новому антибиотику семейства цефалоспоринов — была обнаружена у клинических изолятов метициллинрезистентных Staphylococcus aureus, выделенных еще до внедрения антибиотика в медицинскую практику
et al Proteome dynamics of antibiotic resistant Staphylococcus aureus strains exposed to sub-inhibitory concentrations of beta-lactams
isolates with decreased susceptibility to ceftaroline were reported before the commercial release of the antibiotic. The aim
Summary
Staphylococcus aureus при воздействии субингибирующих концентраций бета-лактамных антибиотиков. Динамика протеома антибиотикорезистентных штаммов Staphylococcus aureus при воздействии субингибирующих концентраций бета-лактамных антибиотиков // Экологическая генетика. CC Устойчивость к цефтаролину — новому антибиотику семейства цефалоспоринов — была обнаружена у клинических изолятов метициллинрезистентных Staphylococcus aureus, выделенных еще до внедрения антибиотика в медицинскую практику. Для выявления механизмов формирования устойчивости к новому антибиотику было проведено сравнение белковых профилей мутантов, устойчивых к цефтаролину, при воздействии субингибирующими концентрациями беталактамных антибиотиков и ванкомицина. Ceftaroline is one of the first cephalosporins with activity against methicillin-resistant Staphylococcus aureus (MRSA), it effectively binds to and inhibits penicillin-binding protein 2a (PBP2a). Однако при изучении коллекций MRSA, полученных еще до внедрения цефтаролина в практику, были обнаружены штаммы, проявляющие устойчивость к этому антибиотику [8]. В качестве контрольного штамма был использован S. aureus ATCC29213 (Remel Culti-Loops, США)
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