Navigating contradictions: Salmonella Typhimurium chemotactic responses to conflicting effector stimuli

Abstract

Many bacteria that colonize the guts of animals use chemotaxis to direct swimming motility and select sites for colonization based on sources of effectors derived from the host, diet, and microbial competitors of the local environ. The complex ecosystem of the gastrointestinal tract contains mixtures of chemoattractants and chemorepellents, but it remains poorly understood how swimming bacteria navigate conflicting signals. The enteric pathogen Salmonella Typhimurium possesses Tsr, a chemoreceptor protein that directs both chemoattraction and chemorepulsion responses, which we employed as a model to study chemotaxis in the presence of conflicting effector stimuli. We investigated how S. Typhimurium responds to human fecal matter, an effector source in the enteric lumen that contains high concentrations of indole, a bacteriostatic chemorepellent produced by the native commensals of the microbiota, and also nutrients such as L-serine, a chemoattractant. The indole concentration in human feces is more than 12-fold the concentration required for half-maximal chemorepulsion, however, we find S. Typhimurium, and various clinical isolates of non-typhoidal S. enterica serovars, are strongly attracted to liquid fecal matter. We further investigated the chemotactic responses of S. Typhimurium to titrations of indole and L-serine and revealed that chemorepulsion to indole is overridden in the presence of excess L-serine. We capture the inversion of these two opposing taxis behaviors in a phenomenon we define as "chemohalation" in which the bacteria organize into a halo around the treatment source with an interior zone of avoidance, which represents a compromise between chemoattraction and chemorepulsion. Growth analyses reveal that the chemotactic responses to these opposing effectors align chemoattraction and chemorepulsion with the relative growth of the bacteria in culture. Hence, our study supports the view that evolution has finely tuned chemotaxis to assess environmental habitability by evaluating the tradeoffs in bacterial growth based on the local combination of effectors.