A genome-wide screening reveals mechanisms by which an enteric pathogen overcome colonization resistance in the gut

Seminar Details
Wednesday, September 30, 2020 - 9:00am to 10:00am


Gustavo Caballero-Flores, Ph.D.
Postdoctoral Fellow
Department of Pathology and Rogel Cancer Center
Michigan Medicine


Virtual Seminar via BlueJeans: https://bluejeans.com/880410398/9042

Use passcode: 9042



The microorganisms naturally inhabiting the gastrointestinal tract, collectively known as the gut “microbiota”, serve as a natural barrier to prevent the invasion and expansion of pathogens, a function termed “colonization resistance”. Several processes have been proposed to explain such a host protection conferred by the microbiota including induction of immune responses, reduction of luminal oxygen, and production of microbiota-derived inhibitory compounds. However, the strategies that bacterial pathogens employ to subvert the colonization resistance conferred by the gut microbiota are largely unknown.

Using a high-density mutant library generated in the mouse pathogen Citrobacter rodentium, we identified specific genes and metabolic pathways that the bacterium requires to colonize the gut of conventionally raised mice, but not germ-free animals. We found that C. rodentium amino acid biosynthesis is important for early pathogen expansion in the presence, but not in the absence, of the microbiota. Mechanistic studies revealed that pathogen amino acid biosynthesis pathways were induced in response to low amounts of amino acids and the presence of the gut microbiota. Reduced amounts of amino acids were found in the gut of conventionally raised mice compared with germ-free animals. Dietary administration of a high protein diet increased levels of amino acids and promoted pathogen colonization in the gut.

Thus, depletion of amino acids by the microbiota limits pathogen colonization, and in turn, the pathogen activates biosynthesis pathways to overcome this nutrient deficiency and to expand in the presence of the gut microbiota. The current study may help design new strategies to prevent or treat enteric infections by targeting pathogen metabolic pathways through dietary or other types of interventions.