Predicting the virulence of MRSA from its genome sequence

• Type of Material: Article
• Authors: Maisem Laabei, University of Bath; Mario Recker, University of Exeter; Justine K. Rudkin, University of Bath; Mona Aldeljawi, University of Bath; Zeynep Gulay, Dokuz Eylul University; Tim J. Sloan, University of Nottingham; Paul Williams, University of Nottingham; Jennifer L. Endres, University of Nebraska Medical Center; Kenneth W. Bayles, University of Nebraska Medical Center; Paul D. Fey, University of Nebraska Medical Center; Vijaya K. Yajjala, University of Nebraska Medical Center; Todd Widhelm, University of Nebraska Medical Center; Erica Hawkins, University of Bath; Katie Lewis, University of Bath; Sara Parfett, University of Bath; Lucy Scowen, University of Bath; Sharon J. Peacock, University of Cambridge; Matthew Holden, Wellcome Trust Sanger Institute; Daniel Wilson, University of Oxford; Timothy Read, Emory University; Jean van den Elsen, University of Bath; Nicholas K. Priest, University of Bath; Edward J. Feil, University of Bath; Laurence D. Hurst, University of Bath; Elisabeth Josefsson, University of Gothenburg; Ruth C. Massey, University of Bath
• Language: English
• Date: 2014-05-01
• Publisher: Cold Spring Harbor Laboratory Press
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Nagarajan et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1101/gr.165415.113
• Title of Journal or Parent Work: Genome Research
• ISSN: 1088-9051
• Volume: 24
• Issue: 5
• Start Page: 839
• End Page: 849
• Grant/Funding Information: M.R. has a Royal Society University Fellowship.; The authors acknowledge financial support via the EC-FP7 program no. 245500 and the BBSRC.
• Keywords: IDENTIFICATION; GENE; Life Sciences & Biomedicine; MYCOBACTERIUM-TUBERCULOSIS; GENETICS & HEREDITY; Biochemistry & Molecular Biology; RESISTANT STAPHYLOCOCCUS-AUREUS; Genetics & Heredity; EVOLUTION; EXPRESSION; Biotechnology & Applied Microbiology; BIOSYNTHESIS; MICROBIOLOGY; BIOCHEMISTRY & MOLECULAR BIOLOGY; BIOTECHNOLOGY & APPLIED MICROBIOLOGY; Science & Technology; TRANSMISSION; ASSOCIATION
• Research Categories: Chemistry, Biochemistry; Biology, Microbiology; Biology, Genetics

Abstract

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.