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The molecular basis for intestinal persistence of Salmonella enterica subspecies I involving gene STM0558

Andrew Bugbee*, Lydia Bogomolnaya, Megan Reynolds, Erin Katribe, Helene Andrews-Polymenis.
College of Veterinary Medicine and College of Medicine, Texas A&M University.  College Station, Texas Andrew Picture


Objective:  Recent experiments have shown that the Salmonella enterica serotype Typhimurium specific STM0557 gene plays a significant role in the pathogen’s ability to persist in murine intestines.  We hypothesize that two upstream genes in the same region, STM0558 and STM0559, may also impact the pathogen’s intestinal persistence ability. 

Procedure:  To evaluate this hypothesis, we generated a deletion mutant of STM0558 and tested it in a murine model.  First, we tested the STM0558 mutant in mice genetically susceptible to Salmonellosis (BALB/c) to evaluate organ colonization.  Second, Salmonella resistant (CBA) mice were used to test intestinal persistence of the STM0558 mutant strain compared to a wild type Salmonella.  Mice were infected orally with a 1:1 mixture (2X108 CFU) of wild type, AJB715 (ATCC 140828s NalR phoN), and an isogenic STM0558 deletion strain (ATCC 14028s NalR STM0558::Kan).  To evaluate organ colonization, BALB/c mice were infected, sacrificed after 4 days, and bacterial CFU of AJB715 vs. STM0558 deleted mutant were enumerated in the spleen, liver, Peyer’s patches, mesenteric lymph nodes, and cecum.  To evaluate intestinal persistence, fecal samples were collected from infected CBA mice and plated every 3 days post-infection to evaluate CFU of wild type vs. STM0558 mutant.

Results:  Strain AJB715 outgrew the STM0558 deletion over the 40 days in the CBA mice, but was similar to the wild type in the ability to colonize organs in the short-term experiments.

Conclusions:  STM0558 mutants are defective in intestinal colonization, indicative that this gene plays an important role in this process.

Impact for Human Medicine:  The determination of the molecular basis for the persistence of Salmonella in the intestines of humans and animals is essential for adequate prevention of Salmonella-induced enterocolitis.