Bacterial host-adaptive evolution overcomes continuous population bottlenecks

Some pathogens have the capacity to undergo host-switches leading to the emergence of new pathogenic clones that are a threat to human and animal health. Following transmission to a new host-species, bacterial populations are influenced by strong population forces due to within-host and transmission bottlenecks causing genetic drift. In theory, populations undergoing periodic bottlenecks exhibit significantly lower fixation rates of beneficial mutations that may limit their capacity for host-adaptation. However, this theoretical understanding, that has not been experimentally tested, belies the fact that many new pathogens emerge as a result of host-jump events. Here we examine the population dynamics of the major human and animal pathogen Staphylococcus aureus in a novel experimental model of host-switching characterized by continuous within-host and transmission bottlenecks. Our comparative genomic and infection competition experiments revealed that contrary to the established dogma, in spite of frequent bottlenecks, mutations accumulated during experimental infection contributed to enhanced fitness in the new host-species. Further, in silico simulations of populations undergoing regular bottlenecks under different selective pressures supported the experimental observation that the fitness gain of beneficial mutations is high enough to overcome genetic drift and sweep through the population. Our findings highlight the remarkable capacity of bacteria to adapt to distinct host niches in the face of powerful antagonistic population forces.