High Order Bacterial Interactions Influence Activity of a Potential Bacteriotherapy Agent

Bacterial replacement therapy has been proposed as a strategy to reduce carriage of antibiotic resistant (ABr) microbes. This type of bacteriotherapy works by providing a strain or a combination of strains capable of outcompeting the ABr microbe from its niche and subsequently occupying the same niche. Here we develop tools that facilitate the identification of potential bacteriotherapy strains and study the influence of environmental factors on their efficacy. We first describe a technique to rapidly study pairwise interactions between bacterial isolates that uses time lapse imaging of bacterial colonies in pairwise combinations. We use this technique to study isolates from healthy human stool against known antibiotic resistance carrying pathogens. We identify a potential bacteriotherapy strain against Enterococcus faecium, a known carrier of vancomycin resistance. The strain is lethal against clinical isolates of E. faecium and it is also hypothesized to occupy a similar metabolic niche. Then we study the influence of third party microbes on the efficacy of our potential bacteriotherapy strain. Interestingly, the presence of certain third party microbes can significantly change the efficacy of our potential bacteriotherapy. Our results begin to describe mechanisms that influence the robustness of our bacteriotherapy strain and shed light on prospective generalizable criteria for the selection of bacterial replacement strains.