Limited adaptive evolution of Staphylococcus aureus during transition from colonization to invasive infection

Abstract

Staphylococcus aureus carriage is a risk factor for invasive infections. Unique genetic elements favoring the transition from colonizing to invasive phenotype have not yet been identified and phenotypic traits are understudied. We therefore assessed pheno- and genotypic profiles of eleven S. aureus isolate pairs sampled from colonized patients simultaneously suffering from invasive S. aureus infections. Ten out of 11 isolate pairs presented the same spa and MLST suggesting colonization as origin for the invasive infection. Systematic analysis of colonizing and invasive isolate pairs showed similar adherence, hemolysis and reproductive fitness properties, minimal genetic differences, identical antibiotic tolerance and bacterial virulence in Galleria mellonella. Our results provide insights into the similar phenotype associated with limited adaptive genetic evolution between the colonizing and invasive isolates. Disruption of the physical barriers mucosa or skin were identified in the majority of patients further emphasizing colonization as a major risk factor for invasive disease. ImportanceS. aureus is a major pathogen of humans causing a wide range of disease. The failure to develop a vaccine and antibiotic warrant the exploration of novel treatment strategies. Asymptomatic colonization of the human nasal passages is a major risk factor for invasive disease and decolonization procedures have shown efficacy in preventing invasive infections. However, the transition of S. aureus from a benign colonizer of the nasal passages to a major pathogen is not well understood and host as well as bacterial properties have been discussed as being relevant for this behavioral change. We conducted a thorough investigation of patient-derived strain pairs reflecting colonizing and invasive isolates in a given patient. Although we identified limited genetic adaptation in certain strains as well as slight differences in adherence capacity of colonizing and invasive isolates, our work suggests that barrier breaches are a key event in the disease continuum of S. aureus.