1887

Abstract

is the aetiologic agent of plague. Without appropriate treatment, the pathogen rapidly causes septicaemia, the terminal and fatal phase of the disease. In order to identify bacterial genes which are essential during septicaemic plague in humans, we performed a transcriptome analysis on the fully virulent CO92 strain grown in either decomplemented human plasma or Luria–Bertani medium, incubated at either 28 or 37 °C and harvested at either the mid-exponential or the stationary growth phase. genes involved in 12 iron-acquisition systems and one iron-storage system (, ) were specifically induced in human plasma. Of these, the and genes (encoding the yersiniabactin siderophore virulence factor and the siderophore transporter, respectively) were induced at 37 °C, i.e. under conditions mimicking the mammalian environment. Growth in human plasma also upregulated genes involved in the synthesis of five fimbrial-like structures (including the Psa virulence factor), and in purine/pyrimidine metabolism (the genes). Genes known to play a role in the virulence of several bacterial pathogens (such as those encoding the Lpp lipoprotein and non-iron metal-uptake proteins) were induced in human plasma, during either the exponential or the stationary phase. Finally, 120 genes encoding proteins of unknown function were upregulated in human plasma. Eleven of these genes were specifically transcribed at 37 °C and may thus represent new virulence factors that are important during the septicaemic phase of human plague.

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2007-09-01
2019-11-18
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References

  1. Achtman, M., Morelli, G., Zhu, P., Wirth, T., Diehl, I., Kusecek, B., Vogler, A. J., Wagner, D. M., Allender, C. J. & other authors ( 2004; ). Microevolution and history of the plague bacillus, Yersinia pestis. Proc Natl Acad Sci U S A 101, 17837–17842.[CrossRef]
    [Google Scholar]
  2. Bearden, S. W. & Perry, R. D. ( 1999; ). The Yfe system of Yersinia pestis transports iron and manganese and is required for full virulence of plague. Mol Microbiol 32, 403–414.[CrossRef]
    [Google Scholar]
  3. Bearden, S. W., Fetherston, J. D. & Perry, R. D. ( 1997; ). Genetic organization of the yersiniabactin biosynthetic region and construction of avirulent mutants in Yersinia pestis. Infect Immun 65, 1659–1668.
    [Google Scholar]
  4. Brubaker, R. R. ( 2000; ). Yersinia pestis and bubonic plague. In The Prokaryotes: an Evolving Electronic Resource for the Microbiological Community. Edited by M. Dworkin, S. Falkow, E. Rosenberg, K.-H. Schleifer & E. Stackelbrandt. New York: Springer.
  5. Campoy, S., Jara, M., Busquets, N., Perez De Rozas, A. M., Badiola, I. & Barbe, J. ( 2002; ). Role of the high-affinity zinc uptake znuABC system in Salmonella enterica serovar Typhimurium virulence. Infect Immun 70, 4721–4725.[CrossRef]
    [Google Scholar]
  6. Chen, Z., Li, B., Zhang, J., Qin, L., Zhou, D., Han, Y., Du, Z., Guo, Z., Song, Y. & Yang, R. ( 2006; ). Quorum sensing affects virulence-associated proteins F1, LcrV, KatY and pH6 etc. of Yersinia pestis as revealed by protein microarray-based antibody profiling. Microbes Infect 8, 2501–2508.[CrossRef]
    [Google Scholar]
  7. Dennis, D. T., Gage, K. L., Gratz, N., Poland, J. D. & Tikhomirov, E. ( 1999; ). Plague manual – epidemiology, distribution, surveillance and control. Geneva: World Health Organization.
  8. Devignat, R. ( 1951; ). Variétés de l'espèce Pasteurella pestis. Nouvelle hypothèse. Bulletin de l'Organisation Mondiale de la Santé 4, 247–263.
    [Google Scholar]
  9. Du, Y., Rosqvist, R. & Forsberg, A. ( 2002; ). Role of fraction 1 antigen of Yersinia pestis in inhibition of phagocytosis. Infect Immun 70, 1453–1460.[CrossRef]
    [Google Scholar]
  10. Flashner, Y., Mamroud, E., Tidhar, A., Ber, R., Aftalion, M., Gur, D., Lazar, S., Zvi, A., Bino, T. & other authors ( 2004; ). Generation of Yersinia pestis attenuated strains by signature-tagged mutagenesis in search of novel vaccine candidates. Infect Immun 72, 908–915.[CrossRef]
    [Google Scholar]
  11. Frangeul, L., Glaser, P., Rusniok, C., Buchrieser, C., Duchaud, E., Dehoux, P. & Kunst, F. ( 2004; ). CAAT-Box, contigs-assembly and annotation tool-box for genome sequencing projects. Bioinformatics 20, 790–797.[CrossRef]
    [Google Scholar]
  12. Garrido, M. E., Bosch, M., Medina, R., Llagostera, M., Perez de Rozas, A. M., Badiola, I. & Barbe, J. ( 2003; ). The high-affinity zinc-uptake system znuACB is under control of the iron-uptake regulator (fur) gene in the animal pathogen Pasteurella multocida. FEMS Microbiol Lett 221, 31–37.[CrossRef]
    [Google Scholar]
  13. Han, Y., Zhou, D., Pang, X., Song, Y., Zhang, L., Bao, J., Tong, Z., Wang, J., Guo, Z. & other authors ( 2004; ). Microarray analysis of temperature-induced transcriptome of Yersinia pestis. Microbiol Immunol 48, 791–805.[CrossRef]
    [Google Scholar]
  14. Hinnebusch, J., Cherepanov, P., Du, Y., Rudolph, A., Dixon, J. D., Schwan, T. & Forsberg, A. ( 2000; ). Murine toxin of Yersinia pestis shows phospholipase D activity but is not required for virulence in mice. Int J Med Microbiol 290, 483–487.[CrossRef]
    [Google Scholar]
  15. Hinnebusch, B. J., Rudolph, A. E., Cherepanov, P., Dixon, J. E., Schwan, T. G. & Forsberg, A. ( 2002; ). Role of Yersinia murine toxin in survival of Yersinia pestis in the midgut of the flea vector. Science 296, 733–735.[CrossRef]
    [Google Scholar]
  16. Hornung, J. M., Jones, H. A. & Perry, R. D. ( 1996; ). The hmu locus of Yersinia pestis is essential for utilization of free haemin and haem-protein complexes as iron sources. Mol Microbiol 20, 725–739.[CrossRef]
    [Google Scholar]
  17. Kim, S., Watanabe, K., Shirahata, T. & Watarai, M. ( 2004; ). Zinc uptake system (znuA locus) of Brucella abortus is essential for intracellular survival and virulence in mice. J Vet Med Sci 66, 1059–1063.[CrossRef]
    [Google Scholar]
  18. Kirillina, O., Bobrov, A. G., Fetherston, J. D. & Perry, R. D. ( 2006; ). Hierarchy of iron uptake systems: Yfu and Yiu are functional in Yersinia pestis. Infect Immun 74, 6171–6178.[CrossRef]
    [Google Scholar]
  19. Lathem, W. W., Crosby, S. D., Miller, V. L. & Goldman, W. E. ( 2005; ). Progression of primary pneumonic plague: a mouse model of infection, pathology and bacterial transcriptional activity. Proc Natl Acad Sci U S A 102, 17786–17791.[CrossRef]
    [Google Scholar]
  20. Li, B., Jiang, L., Song, Q., Yang, J., Chen, Z., Guo, Z., Zhou, D., Du, Z., Song, Y. & other authors ( 2005; ). Protein microarray for profiling antibody responses to Yersinia pestis live vaccine. Infect Immun 73, 3734–3739.[CrossRef]
    [Google Scholar]
  21. Lindler, L. E., Klempner, M. S. & Straley, S. C. ( 1990; ). Yersinia pestis pH 6 antigen: genetic, biochemical and virulence characterization of a protein involved in the pathogenesis of bubonic plague. Infect Immun 58, 2569–2577.
    [Google Scholar]
  22. Marenne, M.-N., Mota, L. J. & Cornelis, G. R. ( 2004; ). The pYV plasmid and the Ysc-Yop type III secretion system. In Yersinia Molecular and Cellular Biology, pp. 319–348. Edited by E. Carniel & B. J. Hinnebusch. Wymondham, UK: Horizon Bioscience.
  23. Motin, V. L., Georgescu, A. M., Fitch, J. P., Gu, P. P., Nelson, D. O., Mabery, S. L., Garnham, J. B., Sokhansanj, B. A., Ott, L. L. & other authors ( 2004; ). Temporal global changes in gene expression during temperature transition in Yersinia pestis. J Bacteriol 186, 6298–6305.[CrossRef]
    [Google Scholar]
  24. Munier-Lehmann, H., Chenal-Francisque, V., Ionescu, M., Chrisova, P., Foulon, J., Carniel, E. & Barzu, O. ( 2003; ). Relationship between bacterial virulence and nucleotide metabolism: a mutation in the adenylate kinase gene renders Yersinia pestis avirulent. Biochem J 373, 515–522.[CrossRef]
    [Google Scholar]
  25. Parkhill, J., Wren, B. W., Thomson, N. R., Titball, R. W., Holden, M. T., Prentice, M. B., Sebaihia, M., James, K. D., Churcher, C. & other authors ( 2001; ). Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413, 523–527.[CrossRef]
    [Google Scholar]
  26. Perry, R. D. & Fetherston, J. ( 2004; ). Iron and heme uptake systems. In Yersinia Molecular and Cellular Biology, pp. 257–283. Edited by E. Carniel & B. J. Hinnebusch. Wymondham, UK: Horizon Bioscience.
  27. Perry, R. D., Shah, J., Bearden, S. W., Thompson, J. M. & Fetherston, J. D. ( 2003; ). Yersinia pestis TonB: role in iron, heme and hemoprotein utilization. Infect Immun 71, 4159–4162.[CrossRef]
    [Google Scholar]
  28. Porat, R., McCabe, W. R. & Brubaker, R. R. ( 1995; ). Lipopolysaccharide-associated resistance to killing of Yersinia by complement. J Endotoxin Res 2, 91–97.
    [Google Scholar]
  29. Sebbane, F., Jarrett, C. O., Gardner, D., Long, D. & Hinnebusch, B. J. ( 2006a; ). Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague. Proc Natl Acad Sci U S A 103, 5526–5530.[CrossRef]
    [Google Scholar]
  30. Sebbane, F., Lemaitre, N., Sturdevant, D. E., Rebeil, R., Virtaneva, K., Porcella, S. F. & Hinnebusch, B. J. ( 2006b; ). Adaptive response of Yersinia pestis to extracellular effectors of innate immunity during bubonic plague. Proc Natl Acad Sci U S A 103, 11766–11771.[CrossRef]
    [Google Scholar]
  31. Sha, J., Fadl, A. A., Klimpel, G. R., Niesel, D. W., Popov, V. L. & Chopra, A. K. ( 2004; ). The two murein lipoproteins of Salmonella enterica serovar Typhimurium contribute to the virulence of the organism. Infect Immun 72, 3987–4003.[CrossRef]
    [Google Scholar]
  32. Sodeinde, O. A., Subrahmanyam, Y. V., Stark, K., Quan, T., Bao, Y. & Goguen, J. D. ( 1992; ). A surface protease and the invasive character of plague. Science 258, 1004–1007.[CrossRef]
    [Google Scholar]
  33. Stanier, R. Y., Ingraham, J. L., Wheelis, M. L. & Painter, P. R. ( 1986; ). The Microbial World, 5th edn. Upper Saddle River, NJ: Prentice-Hall.
  34. Une, T. & Brubaker, R. R. ( 1984; ). In vivo comparison of avirulent Vwa- and Pgm- or Pstr phenotypes of Yersiniae. Infect Immun 43, 895–900.
    [Google Scholar]
  35. Zhou, D., Tong, Z., Song, Y., Han, Y., Pei, D., Pang, X., Zhai, J., Li, M., Cui, B. & other authors ( 2004; ). Genetics of metabolic variations between Yersinia pestis biovars and the proposal of a new biovar, microtus. J Bacteriol 186, 5147–5152.[CrossRef]
    [Google Scholar]
  36. Zhou, D., Qin, L., Han, Y., Qiu, J., Chen, Z., Li, B., Song, Y., Wang, J., Guo, Z. & other authors ( 2006; ). Global analysis of iron assimilation and fur regulation in Yersinia pestis. FEMS Microbiol Lett 258, 9–17.[CrossRef]
    [Google Scholar]
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