Carbon source driven metabolic buffering determines the co-existence of Staphylococcus aureus and Pseudomonas aeruginosa

Pseudomonas aeruginosa and Staphylococcus aureus often co-occur in chronic and intractable infections. Interspecies competition is motivated by their interactions, which increases antibiotic resistance and pathogenicity, resulting in significantly worse healthcare outcomes. This is largely due to changes in both species' growth and metabolism; P. aeruginosa competitively excludes S. aureus by producing small diffusible molecules, which reduces the metabolism and growth of S. aureus. Previous study has shown that differences in nutrient availability, such as carbon sources, in the growing environment affect both the growth and metabolic rate of bacteria. Given that both P. aeruginosa and S. aureus have different preferences for carbon sources, it is possible that the use of such metabolites may perturb the co-existence of these two species. Thus, the objective of this study is to determine how nutritional differences that define the growth environment affect the co-existence of P. aeruginosa and S. aureus. First, we found that when P. aeruginosa and S. aureus were grown independently, carbon sources had differing effects on ATP production when normalized by growth; some carbon sources increased ATP of P. aeruginosa relative to S. aureus, others increased ATP of S. aureus relative to P. aeruginosa. In co-culture, these differences affected the co-existence of both species; carbon sources that increased ATP in S. aureus allowed it to dominate over P. aeruginosa over 24 hours of co-culture. Over the course of 24 hours of co-culture, carbon sources that favored P. aeruginosa consistently allowed it to dominate S. aureus. This was consistent when these communities were grown in continuously mixed, or undisturbed environments. In periodically disturbed environments, however, this relationship does not hold; instead, we discovered that the frequency of disturbance affects co-existence for a given carbon source. Overall, our findings demonstrate how nutrient availability influences polymicrobial community coexistence and may provide novel approaches for rationally modulating polymicrobial community composition.