Staphylococcus aureus Survives in Cystic Fibrosis Macrophages, Forming a Reservoir for Chronic Pneumonia

Abstract

ABSTRACT Staphylococcus aureus plays an important role in sepsis, pneumonia, wound infections, and cystic fibrosis (CF), which is caused by mutations of the cystic fibrosis transmembrane conductance regulator ( Cftr ). Pulmonary S. aureus infections in CF often occur very early and prior to colonization with other pathogens, in particular Pseudomonas aeruginosa . Here, we demonstrate that CF mice are highly susceptible to pulmonary infections with S. aureus and fail to clear the pathogen during infection. S. aureus is internalized by Cftr -deficient macrophages in the lung, but these macrophages are unable to kill intracellular bacteria. This failure might be caused by a defect in the fusion of phagosomes with lysosomes, while this process occurs rapidly in wild-type macrophages and serves to kill intracellular pathogens. Transplantation of infected Cftr -deficient alveolar macrophages into the lungs of noninfected CF mice is sufficient to induce pneumonia. This suggests that intracellular survival of S. aureus in macrophages may allow the pathogen to chronically infect CF lungs.