Metabolic Adaptation in MRSA Pneumonia

RATIONALE: Methicillin-resistant Staphylococcus aureus (MRSA) is a versatile human pathogen associated with diverse types of infections, ranging from benign colonization to sepsis. We postulated that MRSA must undergo specific genotypic and phenotypic changes to cause chronic pulmonary disease. OBJECTIVES: We investigated how MRSA adapts to the human airway to establish chronic infection, as occurs during cystic fibrosis (CF). METHODS: MRSA isolates from patients with cystic fibrosis collected over a four-year period were analyzed by whole-genome sequencing, transcriptional analysis, and metabolic studies. MEASUREMENTS AND MAIN RESULTS: Persistent MRSA infection was associated with staphylococcal metabolic adaptation, not changes in immunogenicity. Adaptation was characterized by selective use of the TCA cycle and generation of biofilm, a means of limiting oxidant stress. Increased transcription of specific metabolic genes was conserved in all host-adapted strains, most notably a 10,000-fold increase in f...