Extended Staphylococcus aureus persistence in cystic fibrosis is associated with bacterial adaptation.

Hirschhausen N, Block D, Bianconi I, Bragonzi A, Birtel J, Lee JC, Dübbers A, Küster P, Kahl J, Peters G, Kahl BC

Zusammenfassung

Staphylococcus aureus often persists in the airways of cystic fibrosis (CF) patients. There is only limited knowledge about bacterial persistence in and adaptation to this new ecological environment. Therefore, we used S. aureus isolates from a unique strain collection, in which all S. aureus isolates recovered from CF patients from two CF centers were stored from more than 150 CF patients for more than a decade. S. aureus early and late isolates from 71 CF patients with long-term staphylococcal colonization of the airways (≥ 5 years) were preselected by genotyping of agr and cap. Identical pairs were subjected to spa-typing and MLST. S. aureus strain pairs of individual patients with the same or closely related spa-type and identical MLST were compared for adaptive changes in important phenotypic and virulence traits. The virulence of three S. aureus strain pairs (early and late isolates) was analyzed in a murine chronic pneumonia model. Strain pairs of 29 individual patients belonged to the same MLST and same or closely related spa-types. The mean persistence of the same clone of S. aureus in 29 CF patients was 8.25 years. Late compared to early isolates were altered in production of capsule (48%), hemolysis (45%), biofilm formation (41%), as well as antibiotic susceptibility (41%), cytotoxicity (34%), colony size (28%), and spa-type (17%). Adaptive changes positively correlated with the length of S. aureus persistence. For seven patients from whom the initial colonizing isolate was recovered, staphylococcal adaptation was most apparent, with capsule production being reduced in five of seven late isolates. In a mouse chronic pneumonia model, all tested isolates strongly induced chronic pneumonia with severe lesions in bronchi and pulmonary parenchyma. Adaptive changes in S. aureus accumulated with the length of persistence in the CF airways, but differed in patients infected with the same S. aureus clonal lineage indicating that individual host factors have an impact on adaptation.