title: The attenuated phenotype of a Salmonella typhimurium flgM mutant is related to expression of FliC flagellin.
abstract: The flgM gene of Salmonella typhimurium encodes a negative regulator of flagellin synthesis that acts by inhibiting the flagellum-specific sigma factor FliA (sigma 28), but only when a mutation in a flagellar basal body, hook, or switch gene is present. We previously showed that FlgM is also necessary for the virulence of S. typhimurium in the mouse model of typhoid fever and proposed that FlgM is required to modulate the activity of the FliA sigma factor, which, in turn, regulates a gene involved in virulence. In this investigation, we observed that (i) the in vitro generation times of flgM mutant and wild-type strains of S. typhimurium were indistinguishable, as were the amounts of flagellin produced by the strains; (ii) the 50% lethal doses of fliA mutant and wild-type strains of S. typhimurium were similar in orally infected mice; and (iii) inactivation of the FliA-regulated flagellin gene fliC in an flgM S. typhimurium mutant resulted in a virulent phenotype. Therefore, we now conclude that expression of the FliC flagellin subunit in an flgM strain is responsible for the attenuated phenotype of an flgM mutant and that FliA does not appear to positively regulate virulence genes in S. typhimurium. Our results suggest that the normal regulation of flagellum synthesis appears to be necessary for virulence and that there may be an advantage conferred in vivo by expression of a particular flagellar phenotype of S. typhimurium.
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hèbert School of Medicine, University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Schmitt
authors.forename: S C
authors.initials: SC
authors.lastname: Darnell
authors.forename: A D
authors.initials: AD
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000235:genetics*; D005408:Flagellin / Q000096:biosynthesis*; D007928:Lethal Dose 50; D051379:Mice; D009154:Mutation; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D012808:Sigma Factor / Q000235:genetics; D014435:Typhoid Fever / Q000382:microbiology; D014774:Virulence / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C064971:FliA protein, Bacteria; C094427:FljB protein, Salmonella; D012097:Repressor Proteins; D012808:Sigma Factor; D005408:Flagellin; C071266:FlgM protein, Bacteria