Naturally occurring polymorphisms in the virulence regulator Rsp modulate Staphylococcus aureus survival in blood and antibiotic susceptibility.

Aishwarya Krishna,Sivaramesh Wigneshweraraj,Matthew T G Holden,Sharon J Peacock,Andrew M Edwards

doi:10.1099/mic.0.000695

Abstract

Nasal colonization by the pathogen Staphylococcus aureus is a risk factor for subsequent infection. Loss of function mutations in the gene encoding the virulence regulator Rsp are associated with the transition of S. aureus from a colonizing isolate to one that causes bacteraemia. Here, we report the identification of several novel activity-altering mutations in rsp detected in clinical isolates, including for the first time, mutations that enhance agr operon activity. We assessed how these mutations affected infection-relevant phenotypes and found loss and enhancement of function mutations to have contrasting effects on S. aureus survival in blood and antibiotic susceptibility. These findings add to the growing body of evidence that suggests S. aureus ‘trades off’ virulence for the acquisition of traits that benefit survival in the host, and indicates that infection severity and treatment options can be significantly affected by mutations in the virulence regulator rsp.

Highlights

Nasal colonization by the pathogen Staphylococcus aureus is a risk factor for subsequent infection
A single mutation resulting in the A204P substitution in the AraC DNA-binding domain of Rsp was found to be the only difference between carriage and bacteraemia isolates from another infected patient [8, 9]
Despite this important role in virulence factor expression, agr dysfunctional strains are often isolated from bloodstream infections, and have been associated with increased duration of and mortality attributed to S. aureus bacteraemia [12,13,14,15,16,17,18]

Summary

Introduction

Nasal colonization by the pathogen Staphylococcus aureus is a risk factor for subsequent infection. Despite this important role in virulence factor expression, agr dysfunctional strains are often isolated from bloodstream infections, and have been associated with increased duration of and mortality attributed to S. aureus bacteraemia [12,13,14,15,16,17,18]. Eight ‘enhancement of function’ mutations were found to significantly increase agr-P3 expression by !120 % of wild-type (Fig. 1c), including that conferring the most common substitution in the collection, D103N.

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Conclusion