RT Journal
A1 Laabei, Maisem
A1 Recker, Mario
A1 Rudkin, Justine K.
A1 Aldeljawi, Mona
A1 Gulay, Zeynep
A1 Sloan, Tim J.
A1 Williams, Paul
A1 Endres, Jennifer L.
A1 Bayles, Kenneth W.
A1 Fey, Paul D.
A1 Yajjala, Vijaya Kumar
A1 Widhelm, Todd
A1 Hawkins, Erica
A1 Lewis, Katie
A1 Parfett, Sara
A1 Scowen, Lucy
A1 Peacock, Sharon J.
A1 Holden, Matthew
A1 Wilson, Daniel
A1 Read, Timothy D.
A1 van den Elsen, Jean
A1 Priest, Nicholas K.
A1 Feil, Edward J.
A1 Hurst, Laurence D.
A1 Josefsson, Elisabet
A1 Massey, Ruth C.
T1 Predicting the virulence of MRSA from its genome sequence
JF Genome Research 
JO Genome Research 
YR 2014 
FD May 01 
VO 24 
IS 5 
SP 839 
OP 849 
DO 10.1101/gr.165415.113 
UL http://genome.cshlp.org/content/24/5/839.abstract 
AB Microbial virulence is a complex and often multifactorial phenotype, intricately linked to a pathogen’s evolutionary trajectory. Toxicity, the ability to destroy host cell membranes, and adhesion, the ability to adhere to human tissues, are the major virulence factors of many bacterial pathogens, including Staphylococcus aureus. Here, we assayed the toxicity and adhesiveness of 90 MRSA (methicillin resistant S. aureus) isolates and found that while there was remarkably little variation in adhesion, toxicity varied by over an order of magnitude between isolates, suggesting different evolutionary selection pressures acting on these two traits. We performed a genome-wide association study (GWAS) and identified a large number of loci, as well as a putative network of epistatically interacting loci, that significantly associated with toxicity. Despite this apparent complexity in toxicity regulation, a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate’s toxicity solely from the genetic signature at these sites. Our results thus highlight the potential of using sequence data to determine clinically relevant parameters and have further implications for understanding the microbial virulence of this opportunistic pathogen.