1887

Abstract

The virulence genes of are modulated during infection by several regulatory systems, and the RcsCDB system is one of the most important of these. The . Typhimurium EG14873 () strain harbours the point mutation, displaying a constitutive activation of this system, which is characterized by mucoid colonies and attenuated virulence phenotypes. In this work, the stability of the mutation was analysed under stress conditions. Under acid and anaerobic stresses, we observed the appearance of small and non-mucoid colonies of the strain. The sequencing of the gene from these colonies showed that the mutation is conserved. Moreover, we found that small colonies were also generated when the wild-type strain grew in acid and anaerobic conditions. It is worth noting that the transition from normal to atypical colonies of both strains only took place after several days of incubation and was not observed during eukaryotic cell infection. Therefore, the appearance of these atypical colonies is a characteristic feature of . Typhimurium strains under stressful situations and does not involve a reversion of the allele and nor does it imply any risk to mammalian cells. Therefore, we propose that the . Typhimurium strain is a good candidate for the development of attenuated vaccines.

Keyword(s): infection , Salmonella and vaccine
Funding
This study was supported by the:
  • Universidad Nacional de Tucumán (Award PIUNT N° D641)
    • Principle Award Recipient: Monica A Delgado
  • Fondo para la Investigación Científica y Tecnológica (Award PICT N°:2015-1819)
    • Principle Award Recipient: Monica A Delgado
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2019-11-12
2024-04-23
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References

  1. Czerkinsky C, Holmgren J. Vaccines against enteric infections for the developing world. Philos Trans R Soc Lond B Biol Sci 2015; 370:20150142 [View Article]
    [Google Scholar]
  2. da Silva AJ, Zangirolami TC, Novo-Mansur MTM, Giordano RdeC, Martins EAL. Live bacterial vaccine vectors: an overview. Braz J Microbiol 2014; 45:1117–1129 [View Article]
    [Google Scholar]
  3. Medina E, Guzmán CA. Use of live bacterial vaccine vectors for antigen delivery: potential and limitations. Vaccine 2001; 19:1573–1580 [View Article]
    [Google Scholar]
  4. Kotton CN, Hohmann EL. Enteric pathogens as vaccine vectors for foreign antigen delivery. Infect Immun 2004; 72:5535–5547 [View Article]
    [Google Scholar]
  5. Lemus JNR, Pérez Baliño N, Kosacoff M. Plan de Abordaje integral de la Enfermedad Diarreica Aguda Y plan de Contingencia de Cólera. Epidemiología Ministerio de Salud de la Nación 2011; 2:8–10
    [Google Scholar]
  6. Murray R, Tataryn J, Pintar K, Thomas MK. Estimates of the burden of illness for eight enteric pathogens associated with animal contact in Canada. Epidemiol Infect 2017; 145:3413–3423 [View Article]
    [Google Scholar]
  7. Mouslim C, Delgado M, Groisman EA. Activation of the RcsC/YojN/RcsB phosphorelay system attenuates Salmonella virulence. Mol Microbiol 2004; 54:386–395 [View Article]
    [Google Scholar]
  8. Majdalani N, Gottesman S. The RCS phosphorelay: a complex signal transduction system. Annu Rev Microbiol 2005; 59:379–405 [View Article]
    [Google Scholar]
  9. Pescaretti MdelasM, Farizano JV, Morero R, Delgado MA. A novel insight on signal transduction mechanism of RcsCDB system in Salmonella enterica serovar Typhimurium. PLoS One 2013; 8:e72527
    [Google Scholar]
  10. Delgado MA, Mouslim C, Groisman EA. The PmrA/PmrB and RcsC/YojN/RcsB systems control expression of the Salmonella O-antigen chain length determinant. Mol Microbiol 2006; 60:39–50 [View Article]
    [Google Scholar]
  11. Farizano JV, Torres MA, Pescaretti MdlM, Delgado MA. The RcsCDB regulatory system plays a crucial role in the protection of Salmonella enterica serovar Typhimurium against oxidative stress. Microbiology 2014; 160:2190–2199 [View Article]
    [Google Scholar]
  12. Fields PI, Swanson RV, Haidaris CG, Heffron F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci USA 1986; 83:5189–5193 [View Article]
    [Google Scholar]
  13. Hoiseth SK, Stocker BAD. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature 1981; 291:238–239 [View Article]
    [Google Scholar]
  14. Mouslim C, Groisman EA. Control of the Salmonella ugd gene by three two-component regulatory systems. Mol Microbiol 2003; 47:335–344 [View Article]
    [Google Scholar]
  15. Sanderson KE, Hessel A, Rudd KE. Genetic map of Salmonella typhimurium, edition VIII. Microbiol Rev 1995; 59:241–303
    [Google Scholar]
  16. Rossi A. Método de determinación de sensibilidad antimicrobiana POR dilución. Clinical and laboratory Standards Institute. Servicios Antimicrobianos 2012; 32:
    [Google Scholar]
  17. Kim W, Surette MG, Kim S. Prevalence of surface swarming behavior in Salmonella . J Bacteriol 2005; 187:6580–6583 [View Article]
    [Google Scholar]
  18. Davis RW, Bolstein D, Roth JR. Advanced Bacterial Genetics: Cold Spring Harbor Laboratory Cold Spring Harbor, NY: 1980
    [Google Scholar]
  19. Miller JH. Experiments in Molecular Genetics New York: Cold Spring Harbor: Cold Spring Harbor Laboratory Press; 1972
    [Google Scholar]
  20. Pichler H, Diridl G, Wolf D. Ciprofloxacin in the treatment of acute bacterial diarrhea: a double blind study. Eur J Clin Microbiol 1986; 5:241–243 [View Article]
    [Google Scholar]
  21. Hooper DC, Wolfson JS, Ng EY, Swartz MN. Mechanisms of action of and resistance to ciprofloxacin. Am J Med 1987; 82:12–20
    [Google Scholar]
  22. Rang CU, Peng AY, Chao L. Temporal dynamics of bacterial aging and rejuvenation. Curr Biol 2011; 21:1813–1816 [View Article]
    [Google Scholar]
  23. Ericsson M, Hanstorp D, Hagberg P, Enger J, Nystrom T. Sorting out bacterial viability with optical tweezers. J Bacteriol 2000; 182:5551–5555 [View Article]
    [Google Scholar]
  24. Nyström T, Starvation NT. Starvation, cessation of growth and bacterial aging. Curr Opin Microbiol 1999; 2:214–219 [View Article]
    [Google Scholar]
  25. Bajaj V, Lucas RL, Hwang C, Lee CA. Co-Ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression. Mol Microbiol 1996; 22:703–714 [View Article]
    [Google Scholar]
  26. Drecktrah D, Knodler LA, Ireland R, Steele-Mortimer O. The mechanism of Salmonella entry determines the vacuolar environment and intracellular gene expression. Traffic 2006; 7:39–51 [View Article]
    [Google Scholar]
  27. Rathman M, Sjaastad MD, Falkow S. Acidification of phagosomes containing Salmonella typhimurium in murine macrophages. Infection and immunity 1996; 64:2765–2773
    [Google Scholar]
  28. Koskiniemi S, Pränting M, Gullberg E, Näsvall J, Andersson DI. Activation of cryptic aminoglycoside resistance in Salmonella enterica . Mol Microbiol 2011; 80:1464–1478 [View Article]
    [Google Scholar]
  29. Chakroun I, Cordero H, Mahdhi A, Morcillo P, Fedhila K et al. Adhesion, invasion, cytotoxic effect and cytokine production in response to atypical Salmonella typhimurium infection. Microb Pathog 2017; 106:40–49 [View Article]
    [Google Scholar]
  30. Dahiya S, Kapil A, Lodha R, Kumar R, Das BK et al. Induction of resistant mutants of Salmonella enterica serotype Typhi under ciprofloxacin selective pressure. Indian J Med Res 2014; 139:746–753
    [Google Scholar]
  31. Wistrand-Yuen E, Knopp M, Hjort K, Koskiniemi S, Berg OG et al. Evolution of high-level resistance during low-level antibiotic exposure. Nat Commun 2018; 9:1599 [View Article]
    [Google Scholar]
  32. Lindgren D. The temperature influence on the spontaneous mutation rate. I. literature review. Hereditas 1972; 70:165–178
    [Google Scholar]
  33. Smits WK, Kuipers OP, Veening J-W. Phenotypic variation in bacteria: the role of feedback regulation. Nat Rev Microbiol 2006; 4:259–271 [View Article]
    [Google Scholar]
  34. Proctor RA BD, McNamara PJ. Electron transport-deficient Staphylococcus aureus small-colony variants as emerging pathogens. Emerging infections 2001; 5:95–110
    [Google Scholar]
  35. Chakroun I, Mahdhi A, Morcillo P, Cordero H, Cuesta A et al. Motility, biofilm formation, apoptotic effect and virulence gene expression of atypical Salmonella Typhimurium outside and inside Caco-2 cells. Microb Pathog 2018; 114:153–162 [View Article]
    [Google Scholar]
  36. Cano DA, Pucciarelli MG, Martínez-Moya M, Casadesús J, García-del Portillo F. Selection of small-colony variants of Salmonella enterica serovar typhimurium in nonphagocytic eucaryotic cells. Infect Immun 2003; 71:3690–3698 [View Article]
    [Google Scholar]
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