Background: Staphylococcus epidermidis, long regarded as an innocuous commensal bacterium of the human skin, is the most frequent cause of nosocomial infections associated with implanted medical devices. This conditional pathogen provides a model of choice to study genome landmarks correlated with the transition between commensalism and pathogenicity. Traditional investigations stress differences in gene content. We focused on conserved genes that have accumulated small mutation differences during the transition. Results: A comparison of strain ATCC12228, a non-biofilm forming, non-infection associated strain and strain RP62A, a methicillin-resistant biofilm clinical isolate revealed consistent variation, mostly single-nucleotide polymorphisms (SNPs), in orthologous genes in addition to the previously investigated global changes in gene clusters. This polymorphism, scattered throughout the genome, may reveal genes that contribute to adaptation of the bacteria to different environmental stimuli, allowing them to shift from commensalism to pathogenicity. SNPs were detected in 931 pairs of orthologs with identical gene length, accounting for approximately 45% of the total pairs of orthologs. Assuming that non-synonymous mutations would mark recent evolution, and hence be associated to the onset of the pathogenic process, analysis of ratios of non-synonymous SNPs vs synonymous SNPs suggested hypotheses about possible pathogenicity determinants. The N/S ratios for virulence factors and surface proteins differed significantly from that of average SNPs. Of those gene pairs, 40 showed a disproportionate distribution of dN vs dS. Among those, the presence of the gene encoding methionine sulfoxide reductase suggested a possible involvement of reactive oxygen species. This led us to uncover that the infection associated strain was significantly more resistant to hydrogen peroxide and paraquat than the environmental strain. Some 16 genes of the list were of unknown function. We could suggest however that they were likely to belong to surface proteins or considered in priority as important for pathogenicity. Conclusion: Our study proposed a novel approach to identify genes involved in pathogenic processes and provided some insight about the molecular mechanisms leading a commensal inhabitant to become an invasive pathogen.
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