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

Abstract

Objectives Methicil l in - resistant Staphylococcus aureus (MRSA) is a leading cause of hospital - associated infection. Acquired r esistance 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 S. aureus methicilin resistance micro evolution 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 CC30 and spa - type t018) of S. aureus that caused an epidemic in the United Kingdom. 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 201 2 . We describe the genetic mechanisms involved in this loss of 40 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 United Kingdom.