Predicting the virulence of MRSA from its genome sequence.
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.
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom;
Maisem
M
Laabei
Mario
M
Recker
Justine K
JK
Rudkin
Mona
M
Aldeljawi
Zeynep
Z
Gulay
Tim J
TJ
Sloan
Paul
P
Williams
Jennifer L
JL
Endres
Kenneth W
KW
Bayles
Paul D
PD
Fey
Vijaya Kumar
VK
Yajjala
Todd
T
Widhelm
Erica
E
Hawkins
Katie
K
Lewis
Sara
S
Parfett
Lucy
L
Scowen
Sharon J
SJ
Peacock
Matthew
M
Holden
Daniel
D
Wilson
Timothy D
TD
Read
Jean
J
van den Elsen
Nicholas K
NK
Priest
Edward J
EJ
Feil
Laurence D
LD
Hurst
Elisabet
E
Josefsson
Ruth C
RC
Massey
D016680:Genome, Bacterial; D055106:Genome-Wide Association Study; D054643:INDEL Mutation; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D014774:Virulence / Q000235:genetics*