Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 61, Issue 3, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02500-16
Keywords
MRSA; mecC; beta-lactams; resistance
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Funding
- (Microbiologia Molecular, Estrutural e Celular) - FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI) [LISBOA-01-0145-FEDER-007660]
- national funds through Fundacao para a Ciencia e a Tecnologia (FCT)
- U.S. Public Health Service award [2 R01 AI457838-15]
- FCT [SFRH/BPD/63992/2009, SFRH/BPD/111697/2015]
- Fundação para a Ciência e a Tecnologia [SFRH/BPD/63992/2009] Funding Source: FCT
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Most methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to beta-lactam antibiotics due to the presence of the mecA gene, encoding an extra penicillin-binding protein (PBP2A) that has low affinity for virtually all beta-lactam antibiotics. Recently, a new resistance determinant-the mecC gene-was identified in S. aureus isolates recovered from humans and dairy cattle. Although having typically low MICs to beta-lactam antibiotics, MRSA strains with the mecC determinant are also capable of expressing high levels of oxacillin resistance when in an optimal genetic background. In order to test the impact of extensive beta-lactam selection on the emergence of mecC-carrying strains with high levels of antibiotic resistance, we exposed the prototype mecC-carrying MRSA strain, LGA251, to increasing concentrations of oxacillin. LGA251 was able to rapidly adapt to high concentrations of oxacillin in growth medium. In such laboratory mutants with increased levels of oxacillin resistance, we identified mutations in genes with no relationship to the mecC regulatory system, indicating that the genetic background plays an important role in the establishment of the levels of oxacillin resistance. Our data also indicate that the stringent stress response plays a critical role in the beta-lactam antibiotic resistance phenotype of MRSA strains carrying the mecC determinant.
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