Respiration of Microbiota-Derived 1,2-propanediol Drives Salmonella Expansion during Colitis

Area of Science:

• Microbiology
• Pathogen-host interactions
• Gut microbiome

Background:

• Intestinal inflammation, often caused by Salmonella enterica serovar Typhimurium, alters the gut environment.
• This altered environment provides increased electron acceptors, supporting pathogen respiration and growth.
• Understanding the specific nutrient sources fueling pathogen expansion is crucial for controlling infections.

Purpose of the Study:

• To identify the carbon sources enabling Salmonella Typhimurium's respiratory growth during intestinal inflammation.
• To investigate the role of 1,2-propanediol utilization in pathogen fitness within the murine gut.
• To determine the influence of host inflammation and gut microbiota composition on Salmonella's ability to utilize 1,2-propanediol.

Main Methods:

• Mouse models of Salmonella Typhimurium infection and intestinal inflammation.
• Germ-free and mono-associated mouse colonization experiments.
• Genetic analysis of Salmonella Typhimurium virulence factors and metabolic genes (pdu genes).
• Assessment of pathogen growth and fitness in vivo.

Main Results:

• Salmonella Typhimurium utilizes 1,2-propanediol, a microbial fermentation product, as a carbon source for respiratory growth in the inflamed mouse intestine.
• 1,2-propanediol utilization is dependent on inflammation induced by Salmonella virulence factors.
• The pathogen employs both aerobic and anaerobic respiration to consume 1,2-propanediol, facilitating expansion in the large intestine.
• While not beneficial in germ-free mice, 1,2-propanediol utilization confers a fitness advantage in the presence of specific commensal bacteria like Bacteroides fragilis and Bacteroides thetaiotaomicron.

Conclusions:

• Intestinal inflammation creates an environment where Salmonella Typhimurium can exploit microbiota-derived fermentation products like 1,2-propanediol.
• This metabolic adaptation allows Salmonella to overcome nutritional competition and expand its population in the gut.
• Targeting the utilization of such fermentation products could be a strategy to control Salmonella infections.