Within‐Host Evolution for the Invasiveness of Commensal Bacteria: an Experimental Study of Bacteremias Resulting fromHaemophilus influenzaeNasal Carriage

BACKGROUND: Many bacteria responsible for clinically relevant disease reside harmlessly in a large fraction of humans. Three explanations have been proposed to account for why these normally commensal bacteria occasionally cause invasive disease: host susceptibility, stochasticity in the host-bacteria interaction, and the evolution of invasive mutants in colonized hosts. Here we test the third of these hypotheses for the rare invasiveness of commensal bacteria: within-host evolution. METHODS AND RESULTS: Using neonatal rats intranasally colonized with pairs of marked Haemophilus influenzae type b strains, we demonstrate that the resulting bacteremias are derived from single organisms. To test the within-host evolution hypothesis we explored the relative ability of bacteria isolated from the blood and nasal passages of bacteremic rats to colonize the nasopharynx and invade the bloodstream. CONCLUSIONS: Our results provide support for within-host evolution as one but not the sole explanation for the invasiveness of these bacteria. We discuss the implications of these results for both the rare invasiveness of commensal bacteria and the general observation that bacteria isolated from the sites of human invasive disease are almost invariably monoclonal.