Dataset Information

Re-emergence of methicillin susceptibility in a resistant lineage of Staphylococcus aureus.

ABSTRACT:

Objectives

MRSA is a leading cause of hospital-associated infection. Acquired resistance is encoded by the mecA gene or its homologue mecC , but little is known about the evolutionary dynamics involved in gain and loss of resistance. The objective of this study was to obtain an expanded understanding of Staphylococcus aureus methicillin resistance microevolution in vivo , by focusing on a single lineage.

Methods

We compared the whole-genome sequences of 231 isolates from a single epidemic lineage [clonal complex 30 (CC30) and spa -type t018] of S. aureus that caused an epidemic in the UK.

Results

We show that resistance to methicillin in this single lineage was gained on at least two separate occasions, one of which led to a clonal expansion around 1995 presumably caused by a selective advantage. Resistance was, however, subsequently lost in vivo by nine strains isolated between 2008 and 2012. We describe the genetic mechanisms involved in this loss of resistance and the imperfect relationship between genotypic and phenotypic resistance.

Conclusions

The recent re-emergence of methicillin susceptibility in this epidemic lineage suggests a significant fitness cost of resistance and reduced selective advantage following the introduction in the mid-2000s of MRSA hospital control measures throughout the UK.

SUBMITTER: Ledda A

PROVIDER: S-EPMC5890754 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Re-emergence of methicillin susceptibility in a resistant lineage of Staphylococcus aureus.

Ledda Alice A Price James R JR Cole Kevin K Llewelyn Martin J MJ Kearns Angela M AM Crook Derrick W DW Paul John J Didelot Xavier X

The Journal of antimicrobial chemotherapy 20170501 5

<h4>Objectives</h4>MRSA is a leading cause of hospital-associated infection. Acquired resistance is encoded by the mecA gene or its homologue mecC , but little is known about the evolutionary dynamics involved in gain and loss of resistance. The objective of this study was to obtain an expanded understanding of Staphylococcus aureus methicillin resistance microevolution in vivo , by focusing on a single lineage.<h4>Methods</h4>We compared the whole-genome sequences of 231 isolates from a single ...[more]

PMID: 28108681

Similar Datasets

Project description:BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear.MethodsHere, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes.ResultsST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role of chp in increasing the virulence potential of ST59 by creating Δchp knockout mutants, confirming that ST59 can carry chp without a measurable impact on fitness.ConclusionsOur results suggest that the ongoing replacement of ST239 by ST59 in China is not associated to higher AMR carriage or biofilm production. However, the increase in ST59 prevalence is concerning since it is linked to a higher potential for virulence, aided by the carriage of the chp gene.

Dataset Information

Re-emergence of methicillin susceptibility in a resistant lineage of Staphylococcus aureus.

Objectives

Methods

Results

Conclusions

Publications

Re-emergence of methicillin susceptibility in a resistant lineage of Staphylococcus aureus.

Similar Datasets

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