Contribution of Asparagine Catabolism to Salmonella Virulence.
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Salmonellae are pathogenic bacteria that cause significant morbidity and mortality in humans worldwide. Salmonellae establish infection and avoid clearance by the immune system by mechanisms that are not well understood. We previously showed that l-asparaginase II produced by Salmonella enterica serovar Typhimurium (S Typhimurium) inhibits T cell responses and mediates virulence. In addition, we previously showed that asparagine deprivation such as that mediated by l-asparaginase II of S Typhimurium causes suppression of activation-induced T cell metabolic reprogramming. Here, we report that STM3997, which encodes a homolog of disulfide bond protein A (dsbA) of Escherichia coli, is required for l-asparaginase II stability and function. Furthermore, we report that l-asparaginase II localizes primarily to the periplasm and acts together with l-asparaginase I to provide S Typhimurium the ability to catabolize asparagine and assimilate nitrogen. Importantly, we determined that, in a murine model of infection, S Typhimurium lacking both l-asparaginase I and II genes competes poorly with wild-type S Typhimurium for colonization of target tissues. Collectively, these results indicate that asparagine catabolism contributes to S Typhimurium virulence, providing new insights into the competition for nutrients at the host-pathogen interface.
author list (cited authors)
McLaughlin, P. A., McClelland, M., Yang, H., Porwollik, S., Bogomolnaya, L., Chen, J., Andrews-Polymenis, H., & van der Velden, A.
complete list of authors
McLaughlin, Patrick A||McClelland, Michael||Yang, Hee-Jeong||Porwollik, Steffen||Bogomolnaya, Lydia||Chen, Juei-Suei||Andrews-Polymenis, Helene||van der Velden, Adrianus WM
editor list (cited editors)