The EAL domain containing protein STM2215 (rtn) is needed during Salmonella infection and has cyclic di-GMP phosphodiesterase activity.

Salmonella Typhimurium gene STM2215 (rtn) is conserved among many enterobacteriaceae. Mutants lacking STM2215 poorly colonized the liver and spleen in intraperitoneal infection of mice and poorly colonized the intestine and deeper tissues in oral infection. These phenotypes were complemented by a wild-type copy of STM2215 provided in trans. STM2215 deletion mutants grew normally in J774A.1 murine macrophages but were unable to invade Caco-2 colonic epithelial cells. Consistent with this finding, mutants in STM2215 produced lower levels of effectors of the TTSS-1. STM2215 is a predicted c-di-GMP phosphodiesterase, but lacks identifiable sensor domains. Biochemical analysis of STM2215 determined that it is located in the inner membrane and has c-di-GMP phosphodiesterase activity in vitro dependent on an intact EAL motif. Unlike some previously identified members of this family, STM2215 did not affect motility, was expressed on plates, and in liquid media at late exponential and early stationary phase during growth. Defined mutations in STM2215 revealed that neither the predicted periplasmic domain nor the anchoring of the protein to the inner membrane is necessary for the activity of this protein during infection. However, the EAL domain of STM2215 is required during infection, suggesting that its phosphodiesterase activity is necessary during infection.