Abstract

BackgroundHorizontal transfer of mobile genetic elements (MGEs) that carry virulence and antimicrobial resistance genes mediates the evolution of methicillin-resistant Staphylococcus aureus, and the emergence of new MRSA clones. Most MRSA lineages show an association with specific MGEs and the evolution of MGE composition following clonal expansion has not been widely studied.ResultsWe investigated the genomes of 1193 S. aureus bloodstream isolates, 1169 of which were MRSA, collected in the UK and the Republic of Ireland between 2001 and 2010. The majority of isolates belonged to clonal complex (CC)22 (n = 923), which contained diverse MGEs including elements that were found in other MRSA lineages. Several MGEs showed variable distribution across the CC22 phylogeny, including two antimicrobial resistance plasmids (pWBG751-like and SAP078A-like, carrying erythromycin and heavy metal resistance genes, respectively), a pathogenicity island carrying the enterotoxin C gene and two phage types Sa1int and Sa6int. Multiple gains and losses of these five MGEs were identified in the CC22 phylogeny using ancestral state reconstruction. Analysis of the temporal distribution of the five MGEs between 2001 and 2010 revealed an unexpected reduction in prevalence of the two plasmids and the pathogenicity island, and an increase in the two phage types. This occurred across the lineage and was not correlated with changes in the relative prevalence of CC22, or of any sub-lineages within in.ConclusionsAncestral state reconstruction coupled with temporal trend analysis demonstrated that epidemic MRSA CC22 has an evolving MGE composition, and indicates that this important MRSA lineage has continued to adapt to changing selective pressure since its emergence.

Highlights

  • Horizontal transfer of mobile genetic elements (MGEs) that carry virulence and antimicrobial resistance genes mediates the evolution of methicillin-resistant Staphylococcus aureus, and the emergence of new Methicillin-resistant Staphylococcus aureus (MRSA) clones

  • Distribution of MGEs identified in MRSA CC22 across S. aureus population We investigated whether MGEs that were detected in MRSA CC22 isolates occur in representatives of other lineages

  • MGE distribution in the context of MRSA CC22 phylogeny The variable frequency of certain MGEs in MRSA CC22 provided an opportunity to investigate the evolutionary dynamics of MGE acquisition and maintenance in this population over a 10-year period. For this we focused on the MGEs that were frequent but not uniformly present in CC22, namely plasmids P1-ermC and P2-hm, pathogenicity island SaPIsec and phages Sa1int and Sa6int (Fig. 2)

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Summary

Introduction

Horizontal transfer of mobile genetic elements (MGEs) that carry virulence and antimicrobial resistance genes mediates the evolution of methicillin-resistant Staphylococcus aureus, and the emergence of new MRSA clones. The pathogenesis of S. aureus infection has been associated with a range of chromosomally-encoded virulence factors. These include exotoxins that damage host cell membranes such as haemolysins and phenol soluble modulins (PSMs), and immune evasion molecules such as protein A and aureolysin [1, 2]. Mobile genetic elements (MGEs) mediate the acquisition of novel virulence factors and are associated with some of the most potent S. aureus virulence molecules, including Panton-Valentine leukocidin and toxic shock syndrome toxin [3]. The most clinically significant example is the Staphylococcal Cassette Chromosome mec (SCCmec) element, which carries the mecA/C gene encoding methicillin resistance [4]

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