ArticlePLoS genetics2017
Evidence for the evolutionary steps leading to mecA-mediated β-lactam resistance in staphylococci.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 80 citations in OpenAlex.
- Isolation and Antibiogram of Staphylococcus aureus Isolated From Bovine Mastitis in Bardaghat Municipality, Nepal.Veterinary medicine and science · 2026Article
- First Report of a Multidrug-ResistantVeterinary sciences · 2026Article
- Antimicrobial Resistance in Veterinary Bacterial Pathogens: Resistance Patterns, Zoonotic Risks and One Health Implications.Pathogens (Basel, Switzerland) · 2026Review
- Comparative Phenotypic and PCR-Based Methicillin Resistance Characterization of Clinical CanineAntibiotics (Basel, Switzerland) · 2026Article
- Review
- Emergence of transferable daptomycin resistance in Gram-positive bacteria.npj antimicrobials and resistance · 2025Article
- In Silico Exploration of Staphylococcal Cassette ChromosomeMicroorganisms · 2025Article
- Zhike Erfang Alleviates MRSA-Induced Pneumonia by Inhibiting TRAF6 and Activating NLRP3 Inflammatory Body.Journal of inflammation research · 2025Article
- Characterization of Staphylococcus aureus isolated from milk samples for their virulence, biofilm, and antimicrobial resistance.Scientific reports · 2024Article
- Genetic Characterization of Antibiotic-ResistantAntibiotics (Basel, Switzerland) · 2024Article
- Photodynamic toluidine blue-gold nanoconjugates as a novel therapeutic forRSC advances · 2023Article
- Genomic Insights into Methicillin-Resistant Staphylococci and Mammaliicocci from Bulk Tank Milk of Dairy Farms in Serbia.Antibiotics (Basel, Switzerland) · 2023Article
- Phage Therapy as an Alternative Treatment Modality for ResistantAntibiotics (Basel, Switzerland) · 2023Review
- Progress in the Prevalence, Classification and Drug Resistance Mechanisms of Methicillin-ResistantInfection and drug resistance · 2023Review
- Antimicrobial resistance and genomic analysis of staphylococci isolated from livestock and farm attendants in Northern Ghana.BMC microbiology · 2022Article
- Staphylococcal Cassette ChromosomeInfection and drug resistance · 2022Article
- Occurrence of Methicillin-Resistant Coagulase-Negative Staphylococci (MRCoNS) and Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2021Article
- Discovery of Pyrrolidine-2,3-diones as Novel Inhibitors ofAntibiotics (Basel, Switzerland) · 2021Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Unconventional Antibacterials and Adjuvants.Accounts of chemical research · 2021Article
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Authors and funding
13 authors at 7 institutions in 6 countries.
Funding
Abstract
The epidemiologically most important mechanism of antibiotic resistance in Staphylococcus aureus is associated with mecA-an acquired gene encoding an extra penicillin-binding protein (PBP2a) with low affinity to virtually all β-lactams. The introduction of mecA into the S. aureus chromosome has led to the emergence of methicillin-resistant S. aureus (MRSA) pandemics, responsible for high rates of mortality worldwide. Nonetheless, little is known regarding the origin and evolution of mecA. Different mecA homologues have been identified in species belonging to the Staphylococcus sciuri group representing the most primitive staphylococci. In this study we aimed to identify evolutionary steps linking these mecA precursors to the β-lactam resistance gene mecA and the resistance phenotype. We sequenced genomes of 106 S. sciuri, S. vitulinus and S. fleurettii strains and determined their oxacillin susceptibility profiles. Single-nucleotide polymorphism (SNP) analysis of the core genome was performed to assess the genetic relatedness of the isolates. Phylogenetic analysis of the mecA gene homologues and promoters was achieved through nucleotide/amino acid sequence alignments and mutation rates were estimated using a Bayesian analysis. Furthermore, the predicted structure of mecA homologue-encoded PBPs of oxacillin-susceptible and -resistant strains were compared. We showed for the first time that oxacillin resistance in the S. sciuri group has emerged multiple times and by a variety of different mechanisms. Development of resistance occurred through several steps including structural diversification of the non-binding domain of native PBPs; changes in the promoters of mecA homologues; acquisition of SCCmec and adaptation of the bacterial genetic background. Moreover, our results suggest that it was exposure to β-lactams in human-created environments that has driven evolution of native PBPs towards a resistance determinant. The evolution of β-lactam resistance in staphylococci highlights the numerous resources available to bacteria to adapt to the selective pressure of antibiotics.
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