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. 1991 Nov 1;174(5):1073–1083. doi: 10.1084/jem.174.5.1073

The Salmonella typhimurium locus mviA regulates virulence in Itys but not Ityr mice: functional mviA results in avirulence; mutant (nonfunctional) mviA results in virulence

PMCID: PMC2119002  PMID: 1940789

Abstract

The virulent Salmonella typhimurium strain WB600 carries the mviA allele of the gene mouse virulence A. As shown here, the virulent phenotype of WB600 is the result of a nonfunctional mviA gene. As compared to the functional allele mviA+, mviA increases virulence in Itys mice, but not in Ityr mice. A specific BglII site, mviA4185, between osmZ and galU, located at approximately 35 min on the salmonella chromosome, was within mviA. Insertion of an antibiotic cassette in the mviA4185 site of mviA+ or the homologous mviA4093 site of mviA DNA resulted in virulence when either cassette was recombined into the chromosome. When mviA and mviA+ were both expressed in the same strain with one carried in the chromosome and the other on a plasmid, avirulence was dominant. Replacement of the mviA allele of strain WB600 using P22 transductions of linked antibiotic cassettes cloned into the chromosome of virulent S. typhimurium strains (SR-11, TML, SL1344, C5, ATCC14028, W118-2, and WB600) showed that all but WB600 contained the avirulent mviA+ allele. Southern hybridizations provided no evidence for a second mviA allele anywhere in the genome of the six non-WB600 strains.

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Selected References

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  1. Benjamin W. H., Jr, Hall P., Roberts S. J., Briles D. E. The primary effect of the Ity locus is on the rate of growth of Salmonella typhimurium that are relatively protected from killing. J Immunol. 1990 Apr 15;144(8):3143–3151. [PubMed] [Google Scholar]
  2. Benjamin W. H., Jr, Turnbough C. L., Jr, Goguen J. D., Posey B. S., Briles D. E. Genetic mapping of novel virulence determinants of Salmonella typhimurium to the region between trpD and supD. Microb Pathog. 1986 Apr;1(2):115–124. doi: 10.1016/0882-4010(86)90014-8. [DOI] [PubMed] [Google Scholar]
  3. Benjamin W. H., Jr, Turnbough C. L., Jr, Posey B. S., Briles D. E. Salmonella typhimurium virulence genes necessary to exploit the Itys/s genotype of the mouse. Infect Immun. 1986 Mar;51(3):872–878. doi: 10.1128/iai.51.3.872-878.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benjamin W. H., Jr, Turnbough C. L., Jr, Posey B. S., Briles D. E. The ability of Salmonella typhimurium to produce the siderophore enterobactin is not a virulence factor in mouse typhoid. Infect Immun. 1985 Nov;50(2):392–397. doi: 10.1128/iai.50.2.392-397.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Briles D. E., Benjamin W. H., Jr, Williams C. A., Davie J. M. A genetic locus responsible for salmonella susceptibility in BSVS mice is not responsible for the limited T-dependent immune responsiveness of BSVS mice. J Immunol. 1981 Sep;127(3):906–911. [PubMed] [Google Scholar]
  7. Briles D. E., Lehmeyer J., Forman C. Phagocytosis and killing of salmonella typhimurium by peritoneal exudate cells. Infect Immun. 1981 Aug;33(2):380–388. doi: 10.1128/iai.33.2.380-388.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brown I. N., Glynn A. A., Plant J. Inbred mouse strain resistance to Mycobacterium lepraemurium follows the Ity/Lsh pattern. Immunology. 1982 Sep;47(1):149–156. [PMC free article] [PubMed] [Google Scholar]
  9. Carter P. B., Collins F. M. The route of enteric infection in normal mice. J Exp Med. 1974 May 1;139(5):1189–1203. doi: 10.1084/jem.139.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chumley F. G., Menzel R., Roth J. R. Hfr formation directed by tn10. Genetics. 1979 Apr;91(4):639–655. doi: 10.1093/genetics/91.4.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Churchward G., Belin D., Nagamine Y. A pSC101-derived plasmid which shows no sequence homology to other commonly used cloning vectors. Gene. 1984 Nov;31(1-3):165–171. doi: 10.1016/0378-1119(84)90207-5. [DOI] [PubMed] [Google Scholar]
  12. Curtiss R., 3rd, Goldschmidt R. M., Fletchall N. B., Kelly S. M. Avirulent Salmonella typhimurium delta cya delta crp oral vaccine strains expressing a streptococcal colonization and virulence antigen. Vaccine. 1988 Apr;6(2):155–160. doi: 10.1016/s0264-410x(88)80020-3. [DOI] [PubMed] [Google Scholar]
  13. Dower W. J., Miller J. F., Ragsdale C. W. High efficiency transformation of E. coli by high voltage electroporation. Nucleic Acids Res. 1988 Jul 11;16(13):6127–6145. doi: 10.1093/nar/16.13.6127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dunlap N. E., Benjamin W. H., Jr, McCall R. D., Jr, Tilden A. B., Briles D. E. A 'safe-site' for Salmonella typhimurium is within splenic cells during the early phase of infection in mice. Microb Pathog. 1991 Apr;10(4):297–310. doi: 10.1016/0882-4010(91)90013-z. [DOI] [PubMed] [Google Scholar]
  15. Edelman R., Levine M. M. Summary of an international workshop on typhoid fever. Rev Infect Dis. 1986 May-Jun;8(3):329–349. doi: 10.1093/clinids/8.3.329. [DOI] [PubMed] [Google Scholar]
  16. Eisenstein T. K., Deakins L. W., Killar L., Saluk P. H., Sultzer B. M. Dissociation of innate susceptibility to Salmonella infection and endotoxin responsiveness in C3HeB/FeJ mice and other strains in the C3H lineage. Infect Immun. 1982 May;36(2):696–703. doi: 10.1128/iai.36.2.696-703.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Eisenstein T. K., Sultzer B. M. Immunity to Salmonella infection. Adv Exp Med Biol. 1983;162:261–296. doi: 10.1007/978-1-4684-4481-0_26. [DOI] [PubMed] [Google Scholar]
  18. Fallon M. T., Benjamin W. H., Jr, Schoeb T. R., Briles D. E. Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth. Infect Immun. 1991 Mar;59(3):852–856. doi: 10.1128/iai.59.3.852-856.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fallon M. T., Schoeb T. R., Benjamin W. H., Jr, Lindsey J. R., Briles D. E. Modulation of resistance to Salmonella typhimurium infection in mice by mouse hepatitis virus (MHV). Microb Pathog. 1989 Feb;6(2):81–91. doi: 10.1016/0882-4010(89)90011-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fields P. I., Swanson R. V., Haidaris C. G., Heffron F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189–5193. doi: 10.1073/pnas.83.14.5189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Finlay B. B., Heffron F., Falkow S. Epithelial cell surfaces induce Salmonella proteins required for bacterial adherence and invasion. Science. 1989 Feb 17;243(4893):940–943. doi: 10.1126/science.2919285. [DOI] [PubMed] [Google Scholar]
  22. Garfinkel D. J., Simpson R. B., Ream L. W., White F. F., Gordon M. P., Nester E. W. Genetic analysis of crown gall: fine structure map of the T-DNA by site-directed mutagenesis. Cell. 1981 Nov;27(1 Pt 2):143–153. doi: 10.1016/0092-8674(81)90368-8. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Gros P., Skamene E., Forget A. Genetic control of natural resistance to Mycobacterium bovis (BCG) in mice. J Immunol. 1981 Dec;127(6):2417–2421. [PubMed] [Google Scholar]
  25. Hashimoto-Gotoh T., Franklin F. C., Nordheim A., Timmis K. N. Specific-purpose plasmid cloning vectors. I. Low copy number, temperature-sensitive, mobilization-defective pSC101-derived containment vectors. Gene. 1981 Dec;16(1-3):227–235. doi: 10.1016/0378-1119(81)90079-2. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Hormaeche C. E. Genetics of natural resistance to salmonellae in mice. Immunology. 1979 Jun;37(2):319–327. [PMC free article] [PubMed] [Google Scholar]
  28. Hormaeche C. E. The in vivo division and death rates of Salmonella typhimurium in the spleens of naturally resistant and susceptible mice measured by the superinfecting phage technique of Meynell. Immunology. 1980 Dec;41(4):973–979. [PMC free article] [PubMed] [Google Scholar]
  29. Hsu H. S. Pathogenesis and immunity in murine salmonellosis. Microbiol Rev. 1989 Dec;53(4):390–409. doi: 10.1128/mr.53.4.390-409.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kadam S. K., Rehemtulla A., Sanderson K. E. Cloning of rfaG, B, I, and J genes for glycosyltransferase enzymes for synthesis of the lipopolysaccharide core of Salmonella typhimurium. J Bacteriol. 1985 Jan;161(1):277–284. doi: 10.1128/jb.161.1.277-284.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lissner C. R., Swanson R. N., O'Brien A. D. Genetic control of the innate resistance of mice to Salmonella typhimurium: expression of the Ity gene in peritoneal and splenic macrophages isolated in vitro. J Immunol. 1983 Dec;131(6):3006–3013. [PubMed] [Google Scholar]
  32. Lissner C. R., Weinstein D. L., O'Brien A. D. Mouse chromosome 1 Ity locus regulates microbicidal activity of isolated peritoneal macrophages against a diverse group of intracellular and extracellular bacteria. J Immunol. 1985 Jul;135(1):544–547. [PubMed] [Google Scholar]
  33. Lowrie D. B., Aber V. R., Carrol M. E. Division and death rates of Salmonella typhimurium inside macrophages: use of penicillin as a probe. J Gen Microbiol. 1979 Feb;110(2):409–419. doi: 10.1099/00221287-110-2-409. [DOI] [PubMed] [Google Scholar]
  34. McIntrye J., Rowley D., Jenkin C. R. The functional heterogeneity of macrophages at the single cell level. Aust J Exp Biol Med Sci. 1967 Dec;45(6):675–680. doi: 10.1038/icb.1967.67. [DOI] [PubMed] [Google Scholar]
  35. Neidhardt F. C., Bloch P. L., Smith D. F. Culture medium for enterobacteria. J Bacteriol. 1974 Sep;119(3):736–747. doi: 10.1128/jb.119.3.736-747.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. O'Brien A. D., Rosenstreich D. L., Taylor B. A. Control of natural resistance to Salmonella typhimurium and Leishmania donovani in mice by closely linked but distinct genetic loci. Nature. 1980 Oct 2;287(5781):440–442. doi: 10.1038/287440a0. [DOI] [PubMed] [Google Scholar]
  37. Plant J. E., Blackwell J. M., O'Brien A. D., Bradley D. J., Glynn A. A. Are the Lsh and Ity disease resistance genes at one locus on mouse chromosome 1? Nature. 1982 Jun 10;297(5866):510–511. doi: 10.1038/297510a0. [DOI] [PubMed] [Google Scholar]
  38. Plant J., Glynn A. A. Genetics of resistance to infection with Salmonella typhimurium in mice. J Infect Dis. 1976 Jan;133(1):72–78. doi: 10.1093/infdis/133.1.72. [DOI] [PubMed] [Google Scholar]
  39. Potter M., O'Brien A. D., Skamene E., Gros P., Forget A., Kongshavn P. A., Wax J. S. A BALB/c congenic strain of mice that carries a genetic locus (Ityr) controlling resistance to intracellular parasites. Infect Immun. 1983 Jun;40(3):1234–1235. doi: 10.1128/iai.40.3.1234-1235.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Que J. U., Hentges D. J. Effect of streptomycin administration on colonization resistance to Salmonella typhimurium in mice. Infect Immun. 1985 Apr;48(1):169–174. doi: 10.1128/iai.48.1.169-174.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Ruvkun G. B., Sundaresan V., Ausubel F. M. Directed transposon Tn5 mutagenesis and complementation analysis of Rhizobium meliloti symbiotic nitrogen fixation genes. Cell. 1982 Jun;29(2):551–559. doi: 10.1016/0092-8674(82)90171-4. [DOI] [PubMed] [Google Scholar]
  42. SCHNEIDER H. A., ZINDER N. D. Nutrition of the host and natural resistance to infection. V. An improved assay employing genetic markers in the double strain inoculation test. J Exp Med. 1956 Feb 1;103(2):207–223. doi: 10.1084/jem.103.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sanderson K. E., Roth J. R. Linkage map of Salmonella typhimurium, Edition VI. Microbiol Rev. 1983 Sep;47(3):410–453. doi: 10.1128/mr.47.3.410-453.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schott R G. The Inheritance of Resistance to SALMONELLA AERTRYCKE in Various Strains of Mice. Genetics. 1932 Mar;17(2):203–229. doi: 10.1093/genetics/17.2.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Taylor B. A., O'Brien A. D. Position on mouse chromosome 1 of a gene that controls resistance to Salmonella typhimurium. Infect Immun. 1982 Jun;36(3):1257–1260. doi: 10.1128/iai.36.3.1257-1260.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Van Gijsegem F., Toussaint A. Chromosome transfer and R-prime formation by an RP4::mini-Mu derivative in Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Proteus mirabilis. Plasmid. 1982 Jan;7(1):30–44. doi: 10.1016/0147-619x(82)90024-5. [DOI] [PubMed] [Google Scholar]
  47. Venneman M. R., Berry L. J. Cell-mediated resistance induced with immunogenic preparations of Salmonella typhimurium. Infect Immun. 1971 Oct;4(4):381–387. doi: 10.1128/iai.4.4.381-387.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  49. Webster L. T. MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN MOUSE TYPHOID INFECTION. J Exp Med. 1923 Jan 31;37(2):231–268. doi: 10.1084/jem.37.2.231. [DOI] [PMC free article] [PubMed] [Google Scholar]

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