Bacterial metabolic remodelling by convergent evolution in response to host niche-dependent nutrient availability

Abstract

AbstractNew pathogens often arise after host jump events between species. However, our understanding of how bacterial pathogens pivot to distinct nutrient availabilities in a new host niche is limited.Staphylococcus aureusis a multi-host pathogen responsible for a global burden of disease in humans and farmed animals. Multiple human-to-bovine host switching events led to the emergence ofS. aureusas a leading cause of intramammary infection in dairy cattle. Here, we employedex vivomilk infections to investigate how bovineS. aureushas adapted to the dairy niche revealing metabolic remodelling including upregulation of genes for lactose utilisation and branched-chain amino acid biosynthesis in response to nutrient availability. Notably, infection of milk by bovineS. aureusresults in a milk clotting phenotype associated with enhanced bacterial growth that is dependent on the protease aureolysin. The same adaptive phenotype has evolved convergently in different bovineS. aureuslineages via mutations in distinct regulatory gene loci that promote enhanced aureolysin expression. Taken together, we have dissected a key adaptive trait for a bacterial pathogen after a host-switch event, involving metabolic remodelling in response to the availability of nutrients. These findings highlight the remarkable evolutionary plasticity ofS. aureusunderpinning its multi-host species tropism.