A single transcriptional regulator is crucial for the adaptation of Staphylococcus aureus to diverse niches.

Adaptation of bacterial pathogens to new hosts often involves the exchange of mobile genetic elements, or generally the highly variable accessory genome. However, adaptation to different niches is often plastic, mediated by conserved pathways in the core genome. The general stress response of most Gram-positive bacteria is a classic case of adaptive plasticity and mediated primarily by the alternative sigma factor B (SigB), a transcriptional regulator. In Staphylococcus aureus, however, sigma factor B appears to have been co-opted to regulate the switch between intracellular and extracellular niches. In the milk-rich extracellular niche of the bovine udder, low sigma factor B activity appears advantageous: during persistent bovine mastitis, narrowly adapted strains entirely deficient in sigma factor B have evolved repeatedly from phenotypically plastic sigma factor B-wild-type strains through various mutations. As we show by transfer of both natural bovine isolates and genetically engineered S. aureus strains from a complex medium to a milk-rich medium, this genetic assimilation is driven by the cost of phenotypic plasticity. Compared with mutated sigma factor B-deficient strains, plastic strains show long time lags in adapting to milk and slower subsequent growth. Overall, we show how a master regulator in the core genome can drive host-specific niche adaptation.