title: Adaptive evolution of Staphylococcus aureus during chronic endobronchial infection of a cystic fibrosis patient.
abstract: The molecular adaptation of Staphylococcus aureus to its host during chronic infection is not well understood. Comparative genome sequencing of 3 S. aureus isolates obtained sequentially over 26 months from the airways of a cystic fibrosis patient, revealed variation in phage content, and genetic polymorphisms in genes which influence antibiotic resistance, and global regulation of virulence. The majority of polymorphisms were isolate-specific suggesting the existence of an heterogeneous infecting population that evolved from a single infecting strain of S. aureus. The genetic variation identified correlated with differences in growth rate, hemolytic activity, and antibiotic sensitivity, implying a profound effect on the ecology of S. aureus. In particular, a high frequency of mutations in loci associated with the alternate transcription factor SigB, were observed. The identification of genes under diversifying selection during long-term infection may inform the design of novel therapeutics for the control of refractory chronic infections.
authors.affiliation: The Roslin Institute and Centre for Infectious Diseases, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, United Kingdom.
authors.forename: Paul R
authors.initials: PR
authors.lastname: McAdam
authors.forename: Anne
authors.initials: A
authors.lastname: Holmes
authors.forename: Kate E
authors.initials: KE
authors.lastname: Templeton
authors.forename: J Ross
authors.initials: JR
authors.lastname: Fitzgerald
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D001980:Bronchi / Q000382:microbiology*; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000382:microbiology*; D019143:Evolution, Molecular; D014644:Genetic Variation; D023281:Genomics; D006801:Humans; D010641:Phenotype; D013211:Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*