2. Universidad Cardenal Herrera-CEU

Genetic transduction is a major evolutionary force that underlies bacterial adaptation.Here we report that the temperate bacteriophages ofStaphylococcusaureusengage in adistinct form of transduction we term lateral transduction. Staphylococcal prophagesdo not follow the previously described excision-replication-packaging pathway but insteadexcise late in their lytic program. Here, DNA packaging initiates in situ from integratedprophages, and large metameric spans including several hundred kilobases of theS.aureusgenome are packaged in phage heads at very high frequency. In situ replication beforeDNA packaging creates multiple prophage genomes so that lateral-transducing particles formduring normal phage maturation, transforming parts of theS.aureuschromosome intohypermobile regions of gene transfer.

Lysogenic induction ends the stable association between a bacteriophage and its host, and the transition to the lytic cycle begins with early prophage excision followed by DNA replication and packaging (ERP). This temporal program is considered universal for P22-like temperate phages, though there is no direct evidence to support the timing and sequence of these events. Here we report that the long-standing ERP program is an observation of the experimentally favored Salmonella phage P22 tsc229 heat-inducible mutant, and that wildtype P22 actually follows the replication-packaging-excision (RPE) program. We find that P22 tsc229 excises early after induction, but P22 delays excision to just before it is detrimental to phage production. This allows P22 to engage in lateral transduction. Thus, at minimal expense to itself, P22 has tuned the timing of excision to balance propagation with lateral transduction, powering the evolution of its host through gene transfer in the interest of selfpreservation.

While many bacterial pathogens are restricted to single host species, some have the capacity to undergo host switches, leading to the emergence of new clones that are a threat to human and animal health. However, the bacterial traits that underpin a multihost ecology are not well understood. Following transmission to a new host, bacterial populations are influenced by powerful forces such as genetic drift that reduce the fixation rate of beneficial mutations, limiting the capacity for host adaptation. Here, we implement a novel experimental model of bacterial host switching to investigate the ability of the multihost pathogen Staphylococcus aureusto adapt to new species under continuous population bottlenecks. We demonstrate that beneficial mutations accumulated during infection can overcome genetic drift and sweep through the population, leading to host adaptation. Our findings highlight the remarkable capacity of some bacteria to adapt to distinct host niches in the face of powerful antagonistic population forces.