title: Expression of STM4467-encoded arginine deiminase controlled by the STM4463 regulator contributes to Salmonella enterica serovar Typhimurium virulence.
abstract: Arginine deiminase (ADI), carbamate kinase (CK), and ornithine transcarbamoylase (OTC) constitute the ADI system. In addition to metabolic functions, the ADI system has been implicated in the virulence of certain pathogens. The pathogenic intracellular bacterium Salmonella enterica serovar Typhimurium possesses the STM4467, STM4466, and STM4465 genes, which are predicted to encode ADI, CK, and OTC, respectively. Here we report that the STM4467 gene encodes an ADI and that ADI activity plays a role in the successful infection of a mammalian host by S. Typhimurium. An STM4467 deletion mutant was defective for replication inside murine macrophages and was attenuated for virulence in mice. We determined that a regulatory protein encoded by the STM4463 gene functions as an activator for STM4467 expression. The expression of the ADI pathway genes was enhanced inside macrophages in a process that required STM4463. Lack of STM4463 impaired the ability of S. Typhimurium to replicate within macrophages. A mutant defective in STM4467-encoded ADI displayed normal production of nitric oxide by macrophages.
authors.affiliation: Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, and Center for Agricultural Biomaterials, Seoul National University, Seoul, South Korea.
authors.forename: Younho
authors.initials: Y
authors.lastname: Choi
authors.forename: Jeongjoon
authors.initials: J
authors.lastname: Choi
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Groisman
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kang
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Shin
authors.forename: Sangryeol
authors.initials: S
authors.lastname: Ryu
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D005810:Multigene Family; D009154:Mutation; D009569:Nitric Oxide / Q000096:biosynthesis; D012481:Salmonella Infections, Animal / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D015534:Trans-Activators; D009569:Nitric Oxide; D001120:Arginine; D006867:Hydrolases; C019723:arginine deiminase