Proteome dynamics of antibiotic resistant Staphylococcus aureus strains exposed to sub-inhibitory concentrations of beta-lactams

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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.

About the authors

Julia V. Sopova

St. Petersburg branch of Vavilov Institute of General Genetics, Russian Academy of Sciences; Saint Petersburg State University

Email: sopova@hotmail.com
ORCID iD: 0000-0002-7825-273X
SPIN-code: 6019-1547

PhD, Researcher, Laboratory of Genetic Models of Human Diseases

Russian Federation, Saint Petersburg; 7/9, Universitetskaya embankment, Saint-Petersburg, 199034

Vladimir V. Gostev

Pediatric Research and Clinical Center for Infectious Diseases

Email: guestvv11@gmail.com
ORCID iD: 0000-0002-3480-8089
SPIN-code: 2431-6231

Researcher, PhD, Department of Medical Microbiology and Molecular Epidemiology

Russian Federation, 9, Professor Popov street, Saint-Petersburg, 197022

Olga S. Kalinogorskaya

Pediatric Research and Clinical Center for Infectious Diseases

Email: kalinogorskaya@bk.ru
ORCID iD: 0000-0003-1419-9068
SPIN-code: 8915-2053

Researcher, PhD, Department of Medical Microbiology and Molecular Epidemiology

Russian Federation, 9, Professor Popov street, Saint-Petersburg, 197022

Anna N. Lykholay

Saint Petersburg State University

Email: a.lykholay@spbu.ru
ORCID iD: 0000-0003-4666-2125
SPIN-code: 7865-8322

MALDI Mass-Spectrometry and Chromatography Specialist, Research Resource Center for Molecular and Cell Technologies

Russian Federation, 7/9, Universitetskaya embankment, Saint-Petersburg, 199034

Sergey V. Sidorenko

Pediatric Research and Clinical Center for Infectious Diseases

Author for correspondence.
Email: sidorserg@gmail.com
ORCID iD: 0000-0003-3550-7875
SPIN-code: 7738-7060

Professor, Head, Department of Medical Microbiology and Molecular Epidemiology

Russian Federation, 9, Professor Popov street, Saint-Petersburg, 197022

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Copyright (c) 2018 Sopova J.V., Gostev V.V., Kalinogorskaya O.S., Lykholay A.N., Sidorenko S.V.

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