Abstract
The adaptation of versatile multi-host pathogens to various hosts and various niches within hosts is often still poorly understood. The alternative Sigma factor B (SigB) is the master regulator of the general stress response of most gram-positive bacteria, which is a classic case of adaptive plasticity. In Staphylococcus aureus , SigB appears co-opted to function as a switch between intracellular and extracellular niches. During bovine mastitis, low SigB-activity confers an advantage in the milk-rich extracellular niche of the bovine udder. We show that narrowly adapted SigB-deficient strains evolved repeatedly from phenotypically plastic SigB-wildtype strains during persistent mastitis. This genetic assimilation appears driven by the cost of phenotypic plasticity: long time lags in adapting to milk and slow growth. Surprisingly, we observe that mutations causing SigB-deficiency allow even human isolates to grow in milk. While host adaptation often proceeds by mobile genetic elements exchanged between strains, we show how a master regulator in the core genome can drive niche adaptation.