Dataset Information

Evolution and single-nucleotide polymorphisms in methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to vancomycin and daptomycin, based on determination of the complete genome.

ABSTRACT: We obtained a series of methicillin-resistant Staphylococcus aureus isolates, including both daptomycin-susceptible strain TD1 and daptomycin-resistant strain TD4, from a patient. We determined the complete genome sequences of TD1 and TD4 using next-generation sequencing, and only four single-nucleotide polymorphisms (SNPs) were identified, one each in capB (E58K), rpoB (H481Y), lytN (I16V), and mprF (V351E). We determined that these four SNPs were sufficient to cause the strains to develop daptomycin, vancomycin, and rifampin resistance.

SUBMITTER: Yamaguchi T

PROVIDER: S-EPMC4432144 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Evolution and single-nucleotide polymorphisms in methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to vancomycin and daptomycin, based on determination of the complete genome.

Yamaguchi Tetsuo T Suzuki Shingo S Okamura Sakiko S Miura Yuri Y Tsukimori Ayaka A Nakamura Itaru I Ito Norihiko N Masuya Anri A Shiina Takashi T Matsumoto Tetsuya T

Antimicrobial agents and chemotherapy 20150316 6

We obtained a series of methicillin-resistant Staphylococcus aureus isolates, including both daptomycin-susceptible strain TD1 and daptomycin-resistant strain TD4, from a patient. We determined the complete genome sequences of TD1 and TD4 using next-generation sequencing, and only four single-nucleotide polymorphisms (SNPs) were identified, one each in capB (E58K), rpoB (H481Y), lytN (I16V), and mprF (V351E). We determined that these four SNPs were sufficient to cause the strains to develop dapt ...[more]

PMID: 25779584

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Project description:The increased prevalence of vancomycin-intermediate Staphylococcus aureus (VISA) is an emerging health care threat. Genome-based comparative methods hold great promise to uncover the genetic basis of the VISA phenotype, which remains obscure. S. aureus isolates were collected from a single individual that presented with recurrent staphylococcal bacteremia at three time points, and the isolates showed successively reduced levels of vancomycin susceptibility. A population genomic approach was taken to compare patient S. aureus isolates with decreasing vancomycin susceptibility across the three time points. To do this, patient isolates were sequenced to high coverage (~500×), and sequence reads were used to model site-specific allelic variation within and between isolate populations. Population genetic methods were then applied to evaluate the overall levels of variation across the three time points and to identify individual variants that show anomalous levels of allelic change between populations. A successive reduction in the overall levels of population genomic variation was observed across the three time points, consistent with a population bottleneck resulting from antibiotic treatment. Despite this overall reduction in variation, a number of individual mutations were swept to high frequency in the VISA population. These mutations were implicated as potentially involved in the VISA phenotype and interrogated with respect to their functional roles. This approach allowed us to identify a number of mutations previously implicated in VISA along with allelic changes within a novel class of genes, encoding LPXTG motif-containing cell-wall-anchoring proteins, which shed light on a novel mechanistic aspect of vancomycin resistance. IMPORTANCE The emergence and spread of antibiotic resistance among bacterial pathogens are two of the gravest threats to public health facing the world today. We report the development and application of a novel population genomic technique aimed at uncovering the evolutionary dynamics and genetic determinants of antibiotic resistance in Staphylococcus aureus. This method was applied to S. aureus cultures isolated from a single patient who showed decreased susceptibility to the vancomycin antibiotic over time. Our approach relies on the increased resolution afforded by next-generation genome-sequencing technology, and it allowed us to discover a number of S. aureus mutations, in both known and novel gene targets, which appear to have evolved under adaptive pressure to evade vancomycin mechanisms of action. The approach we lay out in this work can be applied to resistance to any number of antibiotics across numerous species of bacterial pathogens.

Dataset Information

Evolution and single-nucleotide polymorphisms in methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to vancomycin and daptomycin, based on determination of the complete genome.

Publications

Evolution and single-nucleotide polymorphisms in methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to vancomycin and daptomycin, based on determination of the complete genome.

Similar Datasets

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