Staphylococcus aureus is a major cause of death worldwide, yet 1 in 3 of us carry this bacterium harmlessly in our nose without even knowing it. So, asked Prof. Daniel Wilson in this week’s Departmental Seminar, why do some people get sick with S. aureus while others do not? And what role do genetic changes in S. aureus within a person play in this switch to becoming pathogenic? Together with a team of clinicians, statisticians and biologists, Prof. Wilson has developed statistical methods for Genome Wide Association Studies (GWAS) in bacteria to try to pinpoint the genetic basis of virulence in S. aureus.
Bacterial GWAS methods work by screening the bacterial genome for genetic variants (mutations or genes) that are associated with a given trait, for example whether or not the bacteria made their host sick. This approach must account for the strong population structure that exists within bacterial species to avoid misleadingly inferring thousands of false positives. In doing so, Prof. Wilson’s method can reveal associations that would otherwise be totally obscured by population structure, while simultaneously testing for associations between the trait and different strains of bacteria.
Using these methods, Prof. Wilson and his colleagues found that pyomyositis – an S. aureus infection causing pus-filled abscesses in muscle tissue – can be attributed to the S. aureus PVL toxicity locus. But surprisingly, despite there being more than 150 known virulence factors in S. aureus, these methods find only weak support for any association between the bacterial genome and virulence. One explanation is that the evolution of S. aureus within a person can be sufficiently fast to generate the variants required to enter the bloodstream. By reconstructing the evolution of S. aureus within a person, they identified genetic variants appearing through spontaneous mutation that appear to be advantageous for infection but disadvantageous for onward transmission - perhaps, suggests Prof. Wilson, framing this transition of S. aureus from innocuous bacteria in the nose to the cause of severe infection as a “cancer of the microbiome”.
Bacterial GWAS offers an exciting opportunity to gain new insights into the genetic basis of infectious disease traits and it seems that bacterial evolution within the host may play an important role in traits such as virulence. We’re grateful to Prof. Wilson for an enlightening tour through the challenges and sometimes unexpected discoveries encountered during bacterial GWAS.
Dr Jessica Hedge (@jesshedge1) is a post-doctoral researcher, focusing on the molecular evolution and population dynamics of microbial pathogens.
