Pseudomonas aeruginosa Can Inhibit Growth of Streptococcal Species via Siderophore Production

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 organisms in the CF lung; the presence of P. aeruginosa correlates with lung function decline, and the Streptococcus milleri group (SMG), a subgroup of the viridans streptococci, is associated with exacerbations in patients with CF. Here we characterized 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 that are unable to enhance Streptococcus growth, and we identified the P. aeruginosa pqsL::TnM mutant, which failed to promote growth of Streptococcus 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 overproduces siderophores and thus likely 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. IMPORTANCE Cystic fibrosis (CF) lung infections are increasingly recognized for their polymicrobial nature. These polymicrobial infections may alter the biology of the organisms involved in CF-related infections, leading to changes in growth, virulence, and/or antibiotic tolerance, and could thereby affect patient health and response to treatment. In this study, we demonstrate interactions between P. aeruginosa and streptococci using a coculture model and show that one interaction between these microbes is likely competition for iron. Thus, these data indicate that one CF pathogen may influence the growth of another, and they add to our limited knowledge of polymicrobial interactions in the CF airway.

The Yin and Yang of Streptococcus Lung Infections in Cystic Fibrosis: a Model for Studying Polymicrobial Interactions

“…replicated their genomes (a surrogate for growth) 40-to 60-fold faster than P. aeruginosa (72). This finding would be consistent with the published observations that coculture of Streptococcus with P. aeruginosa enhances the growth of the Streptococcus with no obvious benefit to P. aeruginosa growth (42,67).…”

“…In contrast to the negative interactions described above, recent studies have found that P. aeruginosa can also enhance Streptococcus growth through one or more currently undescribed pathways (42,44,47,48,67). For example, our group demonstrated that P. aeruginosa clinical and laboratory strains can enhance the growth of multiple oral Streptococcus spp., including members of the SMG, through a currently unknown mechanism (67).…”

“…Just as streptococci can impact P. aeruginosa, the converse is true as well. A recent report from our group demonstrated that P. aeruginosa limits Streptococcus growth, likely via iron sequestration, in minimal medium coculture conditions (67). Iron availability in the airway has been demonstrated to range from 0.02 M in healthy controls to levels as high as 8 M in CF patients, and the measured patient-to-patient variability is quite high in CF patient sputum (68)(69)(70)(71).…”

Availability of Zinc Impacts Interactions between Streptococcus sanguinis and Pseudomonas aeruginosa in Coculture

“…polymicrobial communities can have profound and diverse consequences on bacterial growth (8)(9)(10), as well as on disease progression and therapeutic outcomes (6,11).…”

Infect While the Iron is Scarce: Nutrient Explicit Phage-Bacteria Games

“…Microbes in host-pathogen [15], soil [16], and marine systems [17] have adapted to modulate local iron conditions through the evolution of siderophores. Siderophores are small organic molecules with high iron binding affinity [18].…”