Investigation of the growth and survival of Staphylococcus aureus in CFTR-deficient macrophages
Abstract
Staphylococcus aureus and its small colony variants (SCVs) are commonly isolated from the lungs of cystic fibrosis (CF) patients. Although studies have suggested that cystic fibrosis transmembrane regulator (CFTR)-deficient macrophages are diminished in their ability to kill intracellular pathogens, whether this is true for CFTR-deficient macrophages infected with S. aureus or its SCVs is unknown. I employed gentamicin protection and eFluorÔ-670-based proliferation assays to assess the intracellular replication of S. aureus in CFTR inhibitor treated THP-1 and primary human macrophages, and in primary macrophages derived from CF patient blood. My work shows that the susceptibility of CFTR-deficient macrophages to the intracellular growth of wildtype S. aureus USA300 and its SCVs is similar to control macrophages. Importantly, my work demonstrates that SCVs proliferate intracellularly, suggesting that they overcome their auxotrophy through an unknown mechanism. Due to the increasing prevalence of antibiotic-resistant S. aureus, a better understanding of pathogen-host interactions is vital.