A mutation in tdcA attenuates the virulence of Salmonella enterica serovar Typhimurium

• Published in: Molecules and cells Vol. 29; no. 5; pp. 509 - 517
• Main Authors: Lim, S.Y., Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea, Kim, M.J., Seoul National University, Seoul, Republic of Korea, Choi, J.J., Seoul National University, Seoul, Republic of Korea, Ryu, S.R., Seoul National University, Seoul, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Springer Korean Society for Molecular and Cellular Biology 01.05.2010; 한국분자세포생물학회
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cell Biology; Cell Line; Colony Count, Microbial; DNA Replication; DNA, Bacterial - biosynthesis; ESCHERICHIA COLI; Female; Flagella - genetics; Flagella - metabolism; Life Sciences; Liver - microbiology; Liver - pathology; Macrophages - metabolism; Macrophages - microbiology; Macrophages - pathology; Mice; Mice, Inbred BALB C; Operon - genetics; Salmonella; Salmonella Infections, Animal - genetics; Salmonella Infections, Animal - metabolism; Salmonella Infections, Animal - microbiology; Salmonella Infections, Animal - pathology; Salmonella pathogenicity island 2; Salmonella typhi - pathogenicity; Salmonella typhi - physiology; Sequence Deletion - genetics; Spleen - microbiology; Spleen - pathology; ssaG; tdcA; Trans-Activators - genetics; Trans-Activators - metabolism; Virulence - genetics; virulence attenuation; 생물학; pathogenicity island 2 (SPI2); virulence attenuation
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-010-0063-6

The Salmonella tdc operon encodes enzymes belonging to a metabolic pathway that degrades L-serine and L-threonine. The upregulation of the tdc operon and increased virulence of Salmonella grown under oxygenlimiting conditions prompted us to investigate the role of the tdc operon in the pathogenesis of Salmonella Typhimurium. A Salmonella strain carrying a null mutation in tdcA, which encodes the transcriptional activator of the tdc operon, was impaired in mice infected intraperitoneally with the bacterium. In addition, the Salmonella tdcA mutant showed reduced replication compared with the parental strain in cultured animal cells, although their growth rates were similar in various culture media. To understand the function of TdcA in pathogenesis, we performed two-dimensional gel electrophoresis and found that flagellar and PhoP-regulated proteins were affected by the tdcA mutation. The results of β-galactosidase assays and FACS analysis showed that, among the four PhoP-dependent genes tested, the expression of ssaG, which is located in Salmonella pathogenicity island 2 (SPI2), was reduced in the tdcA mutant, especially in the intracellular environment of macrophages. Taken together, our data suggest that tdcA plays an important role in the pathogenesis of Salmonella.