TY  - JOUR
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
Y1  - 2014/05/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 839 
EP  - 849 
DO  - 10.1101/gr.165415.113 
VL  - 24 
IS  - 5 
UR  - http://genome.cshlp.org/content/24/5/839.abstract 
N2  - 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. 
ER  -