Negative interactions and virulence differences drive the dynamics in multispecies bacterial infections

Bacterial infections are often polymicrobial, leading to intricate pathogen-pathogen and pathogen-host interactions. There is increasing interest in studying the molecular basis of pathogen interactions and how such mechanisms impact host morbidity. However, much less is known about the ecological dynamics between pathogens and how they affect virulence and host survival. Here we address these open issues by co-infecting larvae of the insect model host Galleria mellonella with one, two, three or four bacterial species, all of which are opportunistic human pathogens. We found that virulence was always driven by the most virulent species regardless of the number of species and pathogen combinations injected. Moreover, we observed a link between a pathogen’s virulence and its growth within the host. In certain cases, the more virulent pathogen simply outgrew the less virulent pathogen. In other cases, we found evidence for negative interactions between pathogens inside the host, whereby the more virulent pathogen typically won a competition. Taken together, our findings reveal positive links between a pathogen’s growth inside the host, its competitiveness towards other pathogens, and its virulence. Beyond being generalizable across species combinations, our findings suggest that treatment strategies against polymicrobial infections should target the most virulent species.