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bioRxiv · 10.1101/789099

Availability of Zinc Impacts Interactions Between Streptococcus sanguinis and Pseudomonas aeruginosa in Co-culture

Li, K.·Gifford, A. H.·Hampton, T. H.·O'Toole, G.
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Abstract

Airway infections associated with cystic fibrosis (CF) are polymicrobial. We reported previously that clinical isolates of P. aeruginosa 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 Streptococcus sanginuis SK36 whose growth was no longer enhanced by P. aeruginosa PAO1. Mutations in zinc uptake systems of S. sanginuis SK36 reduced growth of these strains by 1-3 log compared to wild-type S. sanginuis SK36 when grown in coculture with P. aeruginosa PA01, while exogenous zinc (0.1-10 m) rescued the coculture defect of zinc uptake mutants of S. sanginuis SK36. Zinc uptake mutants of S. sanginuis SK36 had no obvious growth defect in monoculture. Consistent with a competition for zinc driving coculture dynamics, S. sanginuis SK36 grown in coculture with P. aeruginosa showed increased expression of zinc uptake genes compared to S. sanginuis grown alone. Strains of P. aeruginosa PAO1 defective in zinc transport also supported more robust growth by S. sanginuis compared to coculture with wild-type P. aeruginosa PAO1. An analysis of 118 CF sputum samples revealed that total zinc levels varied from ~5-145 M. At relatively low zinc levels, Pseudomonas and Streptococcus were found in approximately equal abundance; at higher zinc levels, we observed an increasing relative abundance of Pseudomonas and decline of Streptococcus, perhaps as a result of increasing zinc toxicity. Together, our data indicate that the relative abundance of these microbes in the CF airway may be impacted by zinc levels.\n\nIMPORTANCEPolymicrobial infections in CF likely impact patient health, but the mechanism(s) underlying such interactions are poorly understood. Here we show that interactions between Pseudomonas and Streptococcus are modulated by zinc availability using an in vitro model system, 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.

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Li, K., Gifford, A. H., Hampton, T. H., O'Toole, G.. 2019-10-01. Availability of Zinc Impacts Interactions Between Streptococcus sanguinis and Pseudomonas aeruginosa in Co-culture. https://doi.org/10.1101/789099

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