期刊
PLOS GENETICS
卷 13, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1006674
关键词
-
资金
- (Microbiologia Molecular, Estrutural e Celular) - Fundo Europeu de Desenvolvimento Regional through COMPETE - Programa Operacional Competitividade e Internacionalizacao [LISBOA-01-0145-FEDER-007660]
- national funds through Fundacao para a Ciencia e a Tecnologia
- (Unidade de Ciencias Biomoleculares Aplicadas-UCI 610) - national funds from Fundacao para a Ciencia e a Tecnologia [UID/Multi/04378/2013]
- European Regional Development Fund from Fundagao para a Ciencia e a Tecnologia [POCI-01-0145-FEDER-007728, PTDC/BIA-EVF/117507/2010, PTDC/FIS-NAN/0117/ 2014]
- European Society of Clinical Microbiology and Infectious Diseases Research Grants
- US Public Health Service [R01-Al457838-15]
- Fundacao para a Ciencia e a Tecnologia [SFRH / BD / 72675 / 2010]
- Federation of European Microbiology Societies [FEMS-RG-2014-0078]
- Fundação para a Ciência e a Tecnologia [PTDC/BIA-EVF/117507/2010, PTDC/FIS-NAN/0117/2014] Funding Source: FCT
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 beta-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 beta-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 beta-lactams in human-created environments that has driven evolution of native PBPs towards a resistance determinant. The evolution of beta-lactam resistance in staphylococci highlights the numerous resources available to bacteria to adapt to the selective pressure of antibiotics.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据