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Evolutionary trade-offs underlie the multi-faceted virulence of Staphylococcus aureus

Research output: Contribution to journalArticle

Author(s)

Maisem Laabei, Anne-Catrin Uhlemann, Franklin D Lowy, Eloise D Austin, Maho Yokoyama, Khadija Ouadi, Edward Feil, Harry A Thorpe, Barnabas Williams, Mark Perkins, Sharon J Peacock, Stephen R Clarke, Janina Dordel, Matthew Holden, Antonina A Votintseva, Rory Bowden, Derrick W Crook, Bernadette C Young, Daniel J Wilson, Mario Recker & 1 others Ruth C Massey

School/Research organisations

Abstract

Bacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bacteraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high- and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission, highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and transmissibility are critical for understanding the multifaceted nature of bacterial virulence.

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Original languageEnglish
Article numbere1002229
Number of pages21
JournalPLoS Biology
Volume13
Issue number9
DOIs
StatePublished - 2 Sep 2015

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