Regulatory and genomic plasticity of Staphylococcus aureus during persistent colonization and infection.

The major human pathogen Staphylococcus aureus asymptomatically colonizes the anterior nares of humans, but also causes a wide spectrum of diseases including chronic infections such as device-related infections and lung infections in patients with cystic fibrosis (CF). Successful adaptation of the pathogen to the human host is achieved by regulatory mechanisms in the short term and by inheritable shifts in the population over the long term. From direct transcript analysis during infection we deduced that S. aureus is provided with regulatory circuits different than those characterized in vitro. The major virulence regulator agr is not active during chronic infections and agr mutants are frequently isolated from these specimens. Consequently no agr-dependent interference between S. aureus strains was observed during lung infection in CF. The regulator sae seems to be a key factor in the regulatory network controlling gene expression in vivo. S. aureus evolved over the millennia by adapting to the nasal environment and therefore evolutionary changes that can be witnessed over the short term are rare in colonizing strains. In contrast, during chronic infection in CF strong selective pressure is exerted on the pathogen, leading to discernable variations in the clonal lineages. Phage mobilization contributes significantly to genome alteration in S. aureus during infection.