Genome-wide association studies reveal candidate genes associated to bacteraemia caused by ST93-IV CA-MRSA

Abstract

Background: The global emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has seen the dominance of specific clones in different regions around the world with the PVL-positive ST93-IV as the predominant CA-MRSA clone in Australia. In this study we applied a genome-wide association study (GWAS) approach on a collection of Australian ST93-IV MRSA genomes to screen for genetic traits that might have assisted the ongoing transmission of ST93-IV in Australia. We also compared the genomes of ST93-IV bacteraemia and non-bacteraemia isolates to search for potential virulence genes associated with bacteraemia.

Results: Based on single nucleotide polymorphism phylogenetics we revealed two distinct ST93-IV clades circulating concurrently in Australia. One of the clades contained isolates primarily isolated in the northern regions of Australia whilst isolates in the second clade were distributed across the country. Analyses of the ST93-IV genome plasticity over a 15-year period (2002-2017) revealed an observed gain in accessory genes amongst the clone's population. GWAS analysis on the bacteraemia isolates identified two gene candidates that have previously been associated to this kind of infection.

Conclusions: Although this hypothesis was not tested here, it is possible that the emergence of a ST93-IV clade containing additional virulence genes might be related to the high prevalence of ST93-IV infections amongst the indigenous population living in the northern regions of Australia. More importantly, our data also demonstrated that GWAS can reveal candidate genes for further investigations on the pathogenesis and evolution of MRSA strains within a same lineage.

Keywords: Australia; Bacteraemia; GWAS; Phylogenomics; Staphylococcus aureus.

Fig. 1

Rooted Phylogenetic tree of 423 ST93 S. aureus bacteraemia and non-bacteraemia genomes represented as red and white respectively (outer ring). Location is represented by the abbreviation of Australian states and territories: Australian Capital Territory (ACT), New South Wales (NSW), Northern Territory (NT), Queensland (Qld), South Australia (SA), Western Australia (WA), Victoria (Vic) and Tasmania (Tas). Genes present (black) and absence (grey) that correlate with bacteraemia are listed in the order (outer to inner); clfA, hsdM_1, ohrR, acuI, ypuA, hutl_2, entE, soj and entA_2

Fig. 2

Principal Component Analysis of pan-genome gene matrix of ST93-IV isolates. The teal coloured dots represent isolates in clade 1, while the red coloured dots represent isolates in clade 2. Non-clade 1 and 2 isolates are grey coloured dots. The ellipse is generated using the multivariate t- distribution with CI = 95 %