Salmonella enterica serovar Typhimurium mutants unable to convert malate to pyruvate and oxaloacetate are avirulent and immunogenic in BALB/c mice.

Abstract

Previously, we showed that the Salmonella enterica serovar Typhimurium SR-11 tricarboxylic acid (TCA) cycle must operate as a complete cycle for full virulence after oral infection of BALB/c mice (M. Tchawa Yimga, M. P. Leatham, J. H. Allen, D. C. Laux, T. Conway, and P. S. Cohen, Infect. Immun. 74:1130-1140, 2006). In the same study, we showed that for full virulence, malate must be converted to both oxaloacetate and pyruvate. Moreover, it was recently demonstrated that blocking conversion of succinyl-coenzyme A to succinate attenuates serovar Typhimurium SR-11 but does not make it avirulent; however, blocking conversion of succinate to fumarate renders it completely avirulent and protective against subsequent oral infection with the virulent serovar Typhimurium SR-11 wild-type strain (R. Mercado-Lubo, E. J. Gauger, M. P. Leatham, T. Conway, and P. S. Cohen, Infect. Immun. 76:1128-1134, 2008). Furthermore, the ability to convert succinate to fumarate appeared to be required only after serovar Typhimurium SR-11 became systemic. In the present study, evidence is presented that serovar Typhimurium SR-11 mutants that cannot convert fumarate to malate or that cannot convert malate to both oxaloacetate and pyruvate are also avirulent and protective in BALB/c mice. These results suggest that in BALB/c mice, the malate that is removed from the TCA cycle in serovar Typhimurium SR-11 for conversion to pyruvate must be replenished by succinate or one of its precursors, e.g., arginine or ornithine, which might be available in mouse phagocytes.

• Authors: Regino Mercado-Lubo, Mary P Leatham, Tyrrell Conway, Paul S Cohen
• Journal: Infection and immunity (Infect Immun) Vol. 77 Issue 4 Pg. 1397-405 (Apr 2009) ISSN: 1098-5522 [Electronic] United States
• PMID: 19168732 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Culture Media
• Fumarates
• Malates
• Succinates
• Oxaloacetic Acid
• malic acid
• Pyruvic Acid

Topics

• Animals
• Citric Acid Cycle
• Culture Media
• Female
• Fumarates (metabolism)
• Malates (metabolism)
• Mice
• Mice, Inbred BALB C
• Mutation
• Oxaloacetic Acid (metabolism)
• Pyruvic Acid (metabolism)
• Salmonella Infections (immunology, microbiology, mortality)
• Salmonella typhimurium (genetics, growth & development, immunology, pathogenicity)
• Succinates (metabolism)
• Virulence