Interaction networks, ecological stability, and collective antibiotic tolerance in polymicrobial infections

Significance

In many infections, multiple microbial species are present simultaneously. Such polymicrobial infections can be viewed as small microbial ecosystems. Do bacteria in these communities interact with each other? If so, do these interactions affect the stability of the ecosystem, in particular, when antibiotics are present? We focus on urinary tract infections and demonstrate that there are ample ecological interactions between different bacterial species, both in the presence and absence of antibiotics. We further show that they crucially affect ecosystem stability and resilience to environmental perturbations such as antibiotics. Understanding the nature of these polymicrobial communities can point toward ways of disrupting infection ecosystems, which could potentially be used as a new strategy to eradicate infective communities.

Abstract

Polymicrobial infections constitute small ecosystems that accommodate several bacterial species. Commonly, these bacteria are investigated in isolation. However, it is unknown to what extent the isolates interact and whether their interactions alter bacterial growth and ecosystem resilience in the presence and absence of antibiotics. We quantified the complete ecological interaction network for 72 bacterial isolates collected from 23 individuals diagnosed with polymicrobial urinary tract infections and found that most interactions cluster based on evolutionary relatedness. Statistical network analysis revealed that competitive and cooperative reciprocal interactions are enriched in the global network, while cooperative interactions are depleted in the individual host community networks. A population dynamics model parameterized by our measurements suggests that interactions restrict community stability, explaining the observed species diversity of these communities. We further show that the clinical isolates frequently protect each other from clinically relevant antibiotics. Together, these results highlight that ecological interactions are crucial for the growth and survival of bacteria in polymicrobial infection communities and affect their assembly and resilience.