Strain Background, Species Frequency, and Environmental Conditions Are Important in Determining Pseudomonas aeruginosa and Staphylococcus aureus Population Dynamics and Species Coexistence.

Bacterial communities in the environment and in infections are typically diverse, yet we know little about the factors that determine interspecies interactions. Here, we apply concepts from ecological theory to understand how biotic and abiotic factors affect interaction patterns between the two opportunistic human pathogens and , which often cooccur in polymicrobial infections. Specifically, we conducted a series of short- and long-term competition experiments between PAO1 (as our reference strain) and three different strains (Cowan I, 6850, and JE2) at three starting frequencies and under three environmental (culturing) conditions. We found that the competitive ability of strongly depended on the strain background of , whereby dominated against Cowan I and 6850 but not against JE2. In the latter case, both species could end up as winners depending on conditions. Specifically, we observed strong frequency-dependent fitness patterns, including positive frequency dependence, where could dominate JE2 only when common (not when rare). Finally, changes in environmental (culturing) conditions fundamentally altered the competitive balance between the two species in a way that dominance increased when moving from shaken to static environments. Altogether, our results highlight that ecological details can have profound effects on the competitive dynamics between coinfecting pathogens and determine whether two species can coexist or invade each others' populations from a state of rare frequency. Moreover, our findings might parallel certain dynamics observed in chronic polymicrobial infections. Bacterial infections are frequently caused by more than one species, and such polymicrobial infections are often considered more virulent and more difficult to treat than the respective monospecies infections. and are among the most important pathogens in polymicrobial infections, and their cooccurrence is linked to worse disease outcome. There is great interest in understanding how these two species interact and what the consequences for the host are. While previous studies have mainly looked at molecular mechanisms implicated in interactions between and , here we show that ecological factors, such as strain background, species frequency, and environmental conditions, are important elements determining population dynamics and species coexistence patterns. We propose that the uncovered principles also play major roles in infections and, therefore, proclaim that an integrative approach combining molecular and ecological aspects is required to fully understand polymicrobial infections.