Skip to main content
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1996 May;178(10):2911–2915. doi: 10.1128/jb.178.10.2911-2915.1996

The attenuated phenotype of a Salmonella typhimurium flgM mutant is related to expression of FliC flagellin.

C K Schmitt 1, S C Darnell 1, A D O'Brien 1
PMCID: PMC178028  PMID: 8631681

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.

Full Text

The Full Text of this article is available as a PDF (379.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akerley B. J., Miller J. F. Flagellin gene transcription in Bordetella bronchiseptica is regulated by the BvgAS virulence control system. J Bacteriol. 1993 Jun;175(11):3468–3479. doi: 10.1128/jb.175.11.3468-3479.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrews G. P., Maurelli A. T. mxiA of Shigella flexneri 2a, which facilitates export of invasion plasmid antigens, encodes a homolog of the low-calcium-response protein, LcrD, of Yersinia pestis. Infect Immun. 1992 Aug;60(8):3287–3295. doi: 10.1128/iai.60.8.3287-3295.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bäumler A. J., Kusters J. G., Stojiljkovic I., Heffron F. Salmonella typhimurium loci involved in survival within macrophages. Infect Immun. 1994 May;62(5):1623–1630. doi: 10.1128/iai.62.5.1623-1630.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carsiotis M., Stocker B. A., Weinstein D. L., O'Brien A. D. A Salmonella typhimurium virulence gene linked to flg. Infect Immun. 1989 Nov;57(11):3276–3280. doi: 10.1128/iai.57.11.3276-3280.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carsiotis M., Weinstein D. L., Karch H., Holder I. A., O'Brien A. D. Flagella of Salmonella typhimurium are a virulence factor in infected C57BL/6J mice. Infect Immun. 1984 Dec;46(3):814–818. doi: 10.1128/iai.46.3.814-818.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fasano A., Baudry B., Pumplin D. W., Wasserman S. S., Tall B. D., Ketley J. M., Kaper J. B. Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5242–5246. doi: 10.1073/pnas.88.12.5242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feng P., Sugasawara R. J., Schantz A. Identification of a common enterobacterial flagellin epitope with a monoclonal antibody. J Gen Microbiol. 1990 Feb;136(2):337–342. doi: 10.1099/00221287-136-2-337. [DOI] [PubMed] [Google Scholar]
  8. Giannella R. A., Broitman S. A., Zamcheck N. Salmonella enteritis. II. Fulminant diarrhea in and effects on the small intestine. Am J Dig Dis. 1971 Nov;16(11):1007–1013. doi: 10.1007/BF02235013. [DOI] [PubMed] [Google Scholar]
  9. Gillen K. L., Hughes K. T. Negative regulatory loci coupling flagellin synthesis to flagellar assembly in Salmonella typhimurium. J Bacteriol. 1991 Apr;173(7):2301–2310. doi: 10.1128/jb.173.7.2301-2310.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gillen K. L., Hughes K. T. Transcription from two promoters and autoregulation contribute to the control of expression of the Salmonella typhimurium flagellar regulatory gene flgM. J Bacteriol. 1993 Nov;175(21):7006–7015. doi: 10.1128/jb.175.21.7006-7015.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grossman D. A., Witham N. D., Burr D. H., Lesmana M., Rubin F. A., Schoolnik G. K., Parsonnet J. Flagellar serotypes of Salmonella typhi in Indonesia: relationships among motility, invasiveness, and clinical illness. J Infect Dis. 1995 Jan;171(1):212–216. doi: 10.1093/infdis/171.1.212. [DOI] [PubMed] [Google Scholar]
  12. Hoiseth S. K., Stocker B. A. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature. 1981 May 21;291(5812):238–239. doi: 10.1038/291238a0. [DOI] [PubMed] [Google Scholar]
  13. Hughes K. T., Gillen K. L., Semon M. J., Karlinsey J. E. Sensing structural intermediates in bacterial flagellar assembly by export of a negative regulator. Science. 1993 Nov 19;262(5137):1277–1280. doi: 10.1126/science.8235660. [DOI] [PubMed] [Google Scholar]
  14. Ibrahim G. F., Fleet G. H., Lyons M. J., Walker R. A. Method for the isolation of highly purified Salmonella flagellins. J Clin Microbiol. 1985 Dec;22(6):1040–1044. doi: 10.1128/jcm.22.6.1040-1044.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kutsukake K., Iino T. Role of the FliA-FlgM regulatory system on the transcriptional control of the flagellar regulon and flagellar formation in Salmonella typhimurium. J Bacteriol. 1994 Jun;176(12):3598–3605. doi: 10.1128/jb.176.12.3598-3605.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kutsukake K., Ohya Y., Iino T. Transcriptional analysis of the flagellar regulon of Salmonella typhimurium. J Bacteriol. 1990 Feb;172(2):741–747. doi: 10.1128/jb.172.2.741-747.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lockman H. A., Curtiss R., 3rd Salmonella typhimurium mutants lacking flagella or motility remain virulent in BALB/c mice. Infect Immun. 1990 Jan;58(1):137–143. doi: 10.1128/iai.58.1.137-143.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ohnishi K., Kutsukake K., Suzuki H., Lino T. A novel transcriptional regulation mechanism in the flagellar regulon of Salmonella typhimurium: an antisigma factor inhibits the activity of the flagellum-specific sigma factor, sigma F. Mol Microbiol. 1992 Nov;6(21):3149–3157. doi: 10.1111/j.1365-2958.1992.tb01771.x. [DOI] [PubMed] [Google Scholar]
  19. Parsot C., Ménard R., Gounon P., Sansonetti P. J. Enhanced secretion through the Shigella flexneri Mxi-Spa translocon leads to assembly of extracellular proteins into macromolecular structures. Mol Microbiol. 1995 Apr;16(2):291–300. doi: 10.1111/j.1365-2958.1995.tb02301.x. [DOI] [PubMed] [Google Scholar]
  20. Schmitt C. K., Darnell S. C., Tesh V. L., Stocker B. A., O'Brien A. D. Mutation of flgM attenuates virulence of Salmonella typhimurium, and mutation of fliA represses the attenuated phenotype. J Bacteriol. 1994 Jan;176(2):368–377. doi: 10.1128/jb.176.2.368-377.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Strauss E. J. Bacterial pathogenesis. When a turn off is a turn on. Curr Biol. 1995 Jul 1;5(7):706–709. doi: 10.1016/s0960-9822(95)00139-4. [DOI] [PubMed] [Google Scholar]
  22. Yokoseki T., Iino T., Kutsukake K. Negative regulation by fliD, fliS, and fliT of the export of the flagellum-specific anti-sigma factor, FlgM, in Salmonella typhimurium. J Bacteriol. 1996 Feb;178(3):899–901. doi: 10.1128/jb.178.3.899-901.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES