Disaggregation as an interaction mechanism among intestinal bacteria

The gut microbiome contains hundreds of interacting species that together influence host health and development. The mechanisms by which intestinal microbes can interact, however, remain poorly mapped and are often modeled as spatially unstructured competitions for chemical resources. Recent imaging studies examining the zebrafish gut have shown that patterns of aggregation are central to bacterial population dynamics. In this study, we focus on bacterial species of genera Aeromonas and Enterobacter. Two zebrafish gut-derived isolates, Aeromonas ZOR0001 (AE) and Enterobacter ZOR0014 (EN), when mono-associated with the host, are highly aggregated and located primarily in the intestinal midgut. An Aeromonas isolate derived from the commensal strain, Aeromonas-MB4 (AE-MB4), differs from the parental strain in that it is composed mostly of planktonic cells localized to the anterior gut. When challenged by AE-MB4, clusters of EN rapidly fragment into non-motile, slow-growing, dispersed individual cells with overall abundance two orders of magnitude lower than the mono-association value. In the presence of a certain set of additional gut bacterial species, these effects on EN are dampened. In particular, if AE-MB4 invades an already established multi-species community, EN persists in the form of large aggregates. These observations reveal an unanticipated competition mechanism based on manipulation of bacterial spatial organization, namely dissolution of aggregates, and provide evidence that multi-species communities may facilitate stable intestinal co-existence.