Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus

Abstract

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971597/Erratum in: Correction for Pardos de la Gandara et al., "Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus". Antimicrob Agents Chemother. 2018 Jun 26;62(7). pii: e01096-18. doi: 10.1128/AAC.01096-18. Print 2018 Jul. Disponível em: https://aac.asm.org/content/62/7/e01096-18.longMethicillin-resistant Staphylococcus aureus (MRSA) strains carry either a mecA- or a mecC-mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest "archaic" clone of MRSA and in the mecC-carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes (fruB, gmk, hpt, purB, prsA, and relA), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA.This work was financially supported by a US Public Health Service Award 2 R01 AI457838-15 and by project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI), by national funds through FCTFundação para a Ciência e a Tecnologia and project ONEIDA (LISBOA-01-0145-FEDER016417) cofunded by FEEI-“Fundos Europeus Estruturais e de Investimento” from “Programa Operacional Regional Lisboa 2020,” and by national funds from FCT. M.P.D.L.G. was supported by PCORI grant CER-1402-10800 and by funds from the RB Roberts Bacterial Antibiotic Resistance Group (BARG). C.M. was supported by grant SFRH/BPD/111697/2015 from FCT.info:eu-repo/semantics/publishedVersio

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