Deficiency in vitamin B 12 biosynthesis and propionate catabolism impairs anaerobic growth of Salmonella Dublin on ethanolamine and 1,2-propanediol

ABSTRACT Salmonella enterica serovar Dublin is primarily adapted to cattle, and although rarely isolated from humans, infections are often associated with systemically invasive disease. In contrast, the closely related serovar Enteritidis exhibits a broad host range, is highly prevalent in humans, and typically causes self-limiting gastroenteritis. Serovar Typhimurium, which also usually causes localized gastroenteritis, can exploit intestinal compounds such as ethanolamine and 1,2-propanediol to support anaerobic respiration in the inflamed gut, using tetrathionate as an electron acceptor. Genes involved in anaerobic metabolism are frequently degraded in serovars associated with systemic infection. Interestingly, despite its high systemic invasiveness, S . Dublin retains most of these genes, including those required for ethanolamine and 1,2-propanediol utilization. In this study, we compared the growth of S . Dublin and S . Enteritidis clinical isolates under anaerobic conditions with ethanolamine or 1,2-propanediol as sole carbon sources, and their ability to colonize the intestine and trigger inflammation in mice. S . Dublin failed to utilize either compound in minimal medium supplemented with tetrathionate. The defect in ethanolamine catabolism was linked to a deficiency in the cobalamin biosynthesis pathway, as supplementation restored function. In contrast, impairment of 1,2-propanediol metabolism involved not only cobalamin deficiency but also mutations in the propionate degradation pathway. In mice, S . Dublin elicited weaker inflammatory responses and lower intestinal colonization compared to S . Enteritidis. These findings reveal metabolic deficiencies in S . Dublin not predicted by genomic analyses and suggest gene silencing of functions relevant for intestinal colonization but dispensable for systemic growth, representing a possible intermediate stage toward an extraintestinal lifestyle.