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

Alice Ledda1, James R Price2, Kevin Cole2,3

  • 1Department of Infectious Disease Epidemiology, Imperial College London, Norfolk Place, London W2 1PG, UK.

Abstract

Insights

Methicillin-resistant Staphylococcus aureus (MRSA) resistance was gained and lost multiple times within a single lineage. This suggests a fitness cost to MRSA, especially after control measures were implemented.

Area of Science:

  • Microbiology
  • Genetics
  • Evolutionary dynamics

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of hospital-associated infections.
  • The genetic basis of MRSA resistance involves the mecA gene or its homologue mecC.
  • Understanding the evolutionary dynamics of resistance gain and loss in MRSA is crucial.

Purpose of the Study:

  • To investigate the microevolution of methicillin resistance in Staphylococcus aureus within a single lineage.
  • To understand the in vivo evolutionary dynamics of MRSA resistance gain and loss.

Main Methods:

  • Whole-genome sequencing of 231 Staphylococcus aureus isolates from a single epidemic lineage (CC30, spa-type t018) in the UK.
  • Analysis of genetic mechanisms underlying resistance gain and loss.

Main Results:

  • Methicillin resistance was gained at least twice within the studied lineage, with one instance leading to clonal expansion around 1995.
  • Nine strains lost methicillin resistance in vivo between 2008 and 2012.
  • The study identified genetic mechanisms for resistance loss and highlighted an imperfect correlation between genotypic and phenotypic resistance.

Conclusions:

  • The re-emergence of methicillin susceptibility in this MRSA lineage indicates a substantial fitness cost associated with resistance.
  • Reduced selective advantage of MRSA was observed following the implementation of UK-wide hospital control measures in the mid-2000s.

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