Abstract
Cystic Fibrosis (CF) is a genetic disease that causes patients to accumulate thick, dehydrated mucus in the lung and develop chronic, polymicrobial infections due to reduced mucociliary clearance. These chronic polymicrobial infections and subsequent decline in lung function are significant factors in the morbidity and mortality of CF. Pseudomonas aeruginosa and Streptococcus spp. are among the most prevalent pathogens in the CF lung; the presence of P. aeruginosa correlates with lung function decline and the Streptococcus milleri group (SMG) is associated with exacerbations in CF patients. Here we characterize the interspecies interactions that occur between these two genera. We demonstrated that multiple P. aeruginosa laboratory strains and clinical CF isolates promote the growth of multiple SMG strains and oral Streptococci in an in vitro coculture system. We investigated the mechanism by which P. aeruginosa enhances growth of streptococci by screening for mutants of P. aeruginosa PA14 unable to enhance Streptococcus growth, and we identified the P. aeruginosa pqsL::TnM mutant, which failed to promote growth of S. constellatus and S. sanguinis. Characterization of the P. aeruginosa ΔpqsL mutant revealed that this strain cannot promote Streptococcus growth. Our genetic data and growth studies support a model whereby the P. aeruginosa ΔpqsL mutant outcompetes Streptococcus sanguinis for limited iron. We propose a model whereby competition for iron represents one important means of interaction between P. aeruginosa and Streptococcus spp.