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

Airway infections associated with cystic fibrosis (CF) are polymicrobial. We reported previously that clinical isolates of promote the growth of a variety of streptococcal species. To explore the mechanistic basis of this interaction, we performed a genetic screen to identify mutants of SK36 whose growth was no longer enhanced by PAO1. Mutations in the zinc uptake systems of SK36 reduced growth of these strains by 1 to 3 logs compared to that of wild-type SK36 when grown in coculture with PAO1, and exogenous zinc (0.1 to 10 μM) rescued the coculture defect of zinc uptake mutants of SK36. Zinc uptake mutants of SK36 had no obvious growth defect in monoculture. Consistent with competition for zinc driving coculture dynamics, SK36 grown in coculture with showed increased expression of zinc uptake genes compared to that of grown alone. Strains of PAO1 defective in zinc transport also supported ∼2-fold more growth by compared to that in coculture with wild-type PAO1. An analysis of 118 CF sputum samples revealed that total zinc levels varied from ∼5 to 145 μM. At relatively low zinc levels, and spp. were found in approximately equal abundance; at higher zinc levels, we observed a decline in relative abundance of spp., perhaps as a result of increasing zinc toxicity. Together, our data indicate that the relative abundances of these microbes in the CF airway may be impacted by zinc levels. Polymicrobial infections in CF cases likely impact patient health, but the mechanism(s) underlying such interactions is poorly understood. Here, we show using an model system that interactions between and are modulated by zinc availability, and clinical data are consistent with this model. Together with previous studies, our work supports a role for metal homeostasis as a key factor driving microbial interactions.