Swimming motility and chemotaxis control the spatial organization, persistence, and inflammatory activity of a model intestinal pathobiont

Abstract

Understanding the processes that spatially restrict resident gut bacteria and the mechanisms by which disease-causing pathobionts escape this control will open new avenues for microbiome-based therapies. Using live imaging and genetically engineered bacteria, we discovered that flagella-based swimming motility and chemotaxis enable a model Vibrio pathobiont to govern its own spatial organization within the larval zebrafish gut and to persist in the face of the disruptive forces of intestinal flow. Bacterial mutants lacking motility traits became aggregated and lumenally confined, making them susceptible to periodic expulsion from the host. Consequently, non-motile and non-chemotactic mutants experienced large fluctuations in absolute abundance and impaired interbacterial competition. Further, we found that motile bacterial cells induce expression of the proinflammatory cytokine TNF in gut-associated macrophages and the liver. Using inducible genetic switches, we demonstrate that swimming motility can be manipulated in situ to modulate the spatial organization, persistence, and inflammatory activity of gut bacteria.