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Listeria monocytogenes — from saprophyte to intracellular pathogen

Nature Reviews Microbiology volume 7, pages 623–628 (2009)Cite this article

Abstract

Listeria monocytogenes is a bacterium that lives in the soil as a saprophyte but is capable of making the transition into a pathogen following its ingestion by susceptible humans or animals. Recent studies suggest that L. monocytogenes mediates its saprophyte-to-cytosolic-parasite transition through the careful modulation of the activity of a virulence regulatory protein known as PrfA, using a range of environmental cues that include available carbon sources. In this Progress article we describe the regulation of PrfA and its role in the L. monocytogenes transition from the saprophytic stage to the virulent intracellular stage.

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Figure 1: From saprophyte to intracellular pathogen.
Figure 2: A model depicting the influence of carbon transport and metabolism on PrfA-dependent gene expression.
Figure 3: The location of mutations that result in the constitutive activation of PrfA.

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References

  1. Gao, Z., Tseng, C. H., Pei, Z. & Blaser, M. J. Molecular analysis of human forearm superficial skin bacterial biota. Proc. Natl Acad. Sci. USA 104, 2927–2932 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sakamoto, M., Umeda, M. & Benno, Y. Molecular analysis of human oral microbiota. J. Periodont. Res. 40, 277–285 (2005).

    Article  CAS  Google Scholar 

  3. Zoetendal, E. G., Rajilic-Stojanovic, M. & de Vos, W. M. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 57, 1605–1615 (2008).

    Article  CAS  PubMed  Google Scholar 

  4. Gans, J., Wolinsky, M. & Dunbar, J. Computational improvements reveal great bacterial diversity and high metal toxicity in soil. Science 309, 1387–1390 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Gray, M. L. & Killinger, A. H. Listeria monocytogenes and listeric infections. Bacteriol. Rev. 30, 309–382 (1966).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Freitag, N. E. From hot dogs to host cells: how the bacterial pathogen Listeria monocytogenes regulates virulence gene expression. Future Microbiol. 1, 89–101 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Drevets, D. A. & Bronze, M. S. Listeria monocytogenes: epidemiology, human disease, and mechanisms of brain invasion. FEMS Immunol. Med. Microbiol. 53, 151–165 (2008).

    Article  CAS  PubMed  Google Scholar 

  8. Scortti, M., Monzo, H. J., Lacharme-Lora, L., Lewis, D. A. & Vazquez-Boland, J. A. The PrfA virulence regulon. Microbes Infect. 9, 1196–1207 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Thevenot, D., Dernburg, A. & Vernozy-Rozand, C. An updated review of Listeria monocytogenes in the pork meat industry and its products. J. Appl. Microbiol. 101, 7–17 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Hilbi, H., Weber, S. S., Ragaz, C., Nyfeler, Y. & Urwyler, S. Environmental predators as models for bacterial pathogenesis. Environ. Microbiol. 9, 563–575 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Chaturongakul, S., Raengpradub, S., Wiedmann, M. & Boor, K. J. Modulation of stress and virulence in Listeria monocytogenes. Trends Microbiol. 16, 388–396 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lunden, J. M., Autio, T. J. & Korkeala, H. J. Transfer of persistent Listeria monocytogenes contamination between food-processing plants associated with a dicing machine. J. Food Prot. 65, 1129–1133 (2002).

    Article  PubMed  Google Scholar 

  13. Lecuit, M. Human listeriosis and animal models. Microbes Infect. 9, 1216–1225 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Seveau, S., Pizarro-Cerda, J. & Cossart, P. Molecular mechanisms exploited by Listeria monocytogenes during host cell invasion. Microbes Infect. 9, 1167–1175 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Wollert, T. et al. Extending the host range of Listeria monocytogenes by rational protein design. Cell 129, 891–902 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Bakardjiev, A. I., Stacy, B. A., Fisher, S. J. & Portnoy, D. A. Listeriosis in the pregnant guinea pig: a model of vertical transmission. Infect. Immun. 72, 489–497 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Smith, M. A. et al. Dose-response model for Listeria monocytogenes-induced stillbirths in nonhuman primates. Infect. Immun. 76, 726–731 (2008).

    Article  CAS  PubMed  Google Scholar 

  18. Blanot, S. et al. A gerbil model for rhombencephalitis due to Listeria monocytogenes. Microb. Pathog. 23, 39–48 (1997).

    Article  CAS  PubMed  Google Scholar 

  19. Zenewicz, L. A. & Shen, H. Innate and adaptive immune responses to Listeria monocytogenes: a short overview. Microbes Infect. 9, 1208–1215 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pamer, E. G. Immune responses to Listeria monocytogenes. Nature Rev. Immunol. 4, 812–823 (2004).

    Article  CAS  Google Scholar 

  21. Pizarro-Cerda, J. & Cossart, P. Subversion of cellular functions by Listeria monocytogenes. J. Pathol. 208, 215–223 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Schnupf, P. & Portnoy, D. A. Listeriolysin O: a phagosome-specific lysin. Microbes Infect. 9, 1176–1187 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. Kathariou, S., Metz, P., Hof, H. & Goebel, W. Tn916-induced mutations in the hemolysin determinant affecting virulence of Listeria monocytogenes. J. Bacteriol. 169, 1291–1297 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Vazquez-Boland, J. et al. Nucleotide sequence of the lecithinase operon of Listeria monocytogenes and possible role of lecithinase in cell-to-cell spread. Infect. Immun. 60, 219–230 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Mengaud, J., Braun-Breton, C. & Cossart, P. Identification of phosphatidylinositol-specific phospholipase C activity in Listeria monocytogenes: a novel type of virulence factor? Mol. Microbiol. 5, 367–372 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. Camilli, A., Goldfine, H. & Portnoy, D. A. Listeria monocytogenes mutants lacking phosphatidylinositol-specific phospholipase C are avirulent. J. Exp. Med. 173, 751–754 (1991).

    Article  CAS  PubMed  Google Scholar 

  27. Joseph, B. & Goebel, W. Life of Listeria monocytogenes in the host cells' cytosol. Microbes Infect. 9, 1188–1195 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Marquis, H., Bouwer, H. G., Hinrichs, D. J. & Portnoy, D. A. Intracytoplasmic growth and virulence of Listeria monocytogenes auxotrophic mutants. Infect. Immun. 61, 3756–3760 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. O'Riordan, M., Moors, M. A. & Portnoy, D. A. Listeria intracellular growth and virulence require host-derived lipoic acid. Science 302, 462–464 (2003).

    Article  CAS  PubMed  Google Scholar 

  30. Yeung, P. S., Na, Y., Kreuder, A. J. & Marquis, H. Compartmentalization of the broad-range phospholipase C activity to the spreading vacuole is critical for Listeria monocytogenes virulence. Infect. Immun. 75, 44–51 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. Scortti, M. et al. Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular basis of an antimicrobial in vitro–in vivo paradox. Nature Med. 12, 515–517 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Port, G. C. & Freitag, N. E. Identification of novel Listeria monocytogenes secreted virulence factors following mutational activation of the central virulence regulator, PrfA. Infect. Immun. 75, 5886–5897 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Begley, M., Sleator, R. D., Gahan, C. G. & Hill, C. Contribution of three bile-associated loci, bsh, pva, and btlB, to gastrointestinal persistence and bile tolerance of Listeria monocytogenes. Infect. Immun. 73, 894–904 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hardy, J. et al. Extracellular replication of Listeria monocytogenes in the murine gall bladder. Science 303, 851–853 (2004).

    Article  CAS  PubMed  Google Scholar 

  35. Dussurget, O. et al. Listeria monocytogenes bile salt hydrolase is a PrfA-regulated virulence factor involved in the intestinal and hepatic phases of listeriosis. Mol. Microbiol. 45, 1095–1106 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Gahan, C. G. & Hill, C. Gastrointestinal phase of Listeria monocytogenes infection. J. Appl. Microbiol. 98, 1345–1353 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Freitag, N. E., Rong, L. & Portnoy, D. A. Regulation of the prfA transcriptional activator of Listeria monocytogenes: multiple promoter elements contribute to intracellular growth and cell-to-cell spread. Infect. Immun. 61, 2537–2544 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Freitag, N. E. & Portnoy, D. A. Dual promoters of the Listeria monocytogenes prfA transcriptional activator appear essential in vitro but are redundant in vivo. Mol. Microbiol. 12, 845–853 (1994).

    Article  CAS  PubMed  Google Scholar 

  39. Johansson, J. et al. An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110, 551 (2002).

    Article  PubMed  Google Scholar 

  40. Cheng, L. W. & Portnoy, D. A. Drosophila S2 cells: an alternative infection model for Listeria monocytogenes. Cell. Microbiol. 5, 875–885 (2003).

    Article  CAS  PubMed  Google Scholar 

  41. Cheng, L. W. et al. Use of RNA interference in Drosophila S2 cells to identify host pathways controlling compartmentalization of an intracellular pathogen. Proc. Natl Acad. Sci. USA 102, 13646–13651 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mansfield, B. E., Dionne, M. S., Schneider, D. S. & Freitag, N. E. Exploration of host–pathogen interactions using Listeria monocytogenes and Drosophila melanogaster. Cell. Microbiol. 5, 901–911 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Agaisse, H. et al. Genome-wide RNAi screen for host factors required for intracellular bacterial infection. Science 309, 1248–1251 (2005).

    Article  CAS  PubMed  Google Scholar 

  44. Renzoni, A., Klarsfeld, A., Dramsi, S. & Cossart, P. Evidence that PrfA, the pleitropic activator of virulence genes in Listeria monocytogenes, can be present but inactive. Infect. Immun. 65, 1515–1518 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Lampidis, R., Gross, R., Sokolovic, Z., Goebel, W. & Kreft, J. The virulence regulator protein of Listeria ivanovii is highly homologous to PrfA from Listeria monocytogenes and both belong to the Crp–Fnr family of transcription regulators. Mol. Microbiol. 13, 141–151 (1994).

    Article  CAS  PubMed  Google Scholar 

  46. Vega, Y. et al. Functional similarities between the Listeria monocytogenes virulence regulator PrfA and cyclic AMP receptor protein: the PrfA* (Gly145Ser) mutation increases binding affinity for target DNA. J. Bacteriol. 180, 6655–6660 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Korner, H., Sofia, H. J. & Zumft, W. G. Phylogeny of the bacterial superfamily of Crp–Fnr transcription regulators: exploiting the metabolic spectrum by controlling alternative gene programs. FEMS Microbiol. Rev. 27, 559–592 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Milenbachs, A. A., Brown, D. P., Moors, M. & Youngman, P. Carbon-source regulation of virulence gene expression in Listeria monocytogenes. Mol. Microbiol. 23, 1075–1085 (1997).

    Article  CAS  PubMed  Google Scholar 

  49. Park, S. F., Stewart, G. S. A. B. & Kroll, R. G. The use of bacterial luciferase for monitoring the environmental regulation of expression of genes encoding virulence factors in Listeria monocytogenes. J. Gen. Microbiol. 138, 2619–2627 (1992).

    Article  CAS  PubMed  Google Scholar 

  50. Chico-Calero, I. et al. Hpt, a bacterial homolog of the microsomal glucose-6-phosphate translocase, mediates rapid intracellular proliferation in Listeria. Proc. Natl Acad. Sci. USA 99, 431–436 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Park, S. F. & Kroll, R. G. Expression of listeriolysin and phosphatidylinositol-specific phospholipase C is repressed by the plant-derived molecule cellobiose in Listeria monocytogenes. Mol. Microbiol. 8, 653–661 (1993).

    Article  CAS  PubMed  Google Scholar 

  52. Joseph, B. et al. Identification of Listeria monocytogenes genes contributing to intracellular replication by expression profiling and mutant screening. J. Bacteriol. 188, 556–568 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Eylert, E. et al. Carbon metabolism of Listeria monocytogenes growing inside macrophages. Mol. Microbiol. 69, 1008–1017 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Gorke, B. & Stulke, J. Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nature Rev. Microbiol. 6, 613–624 (2008).

    Article  CAS  Google Scholar 

  55. Joseph, B. et al. Glycerol metabolism and PrfA activity in Listeria monocytogenes. J. Bacteriol. 190, 5412–5430 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Stoll, R., Mertins, S., Joseph, B., Muller-Altrock, S. & Goebel, W. Modulation of PrfA activity in Listeria monocytogenes upon growth in different culture media. Microbiology 154, 3856–3876 (2008).

    Article  CAS  PubMed  Google Scholar 

  57. Eiting, M., Hageluken, G., Schubert, W. D. & Heinz, D. W. The mutation G145S in PrfA, a key virulence regulator of Listeria monocytogenes, increases DNA-binding affinity by stabilizing the HTH motif. Mol. Microbiol. 56, 433–446 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Miner, M. D., Port, G. C., Bouwer, H. G., Chang, J. C. & Freitag, N. E. A novel prfA mutation that promotes Listeria monocytogenes cytosol entry but reduces bacterial spread and cytotoxicity. Microb. Pathog. 45, 273–281 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Miner, M. D., Port, G. C. & Freitag, N. E. Functional impact of mutational activation on the Listeria monocytogenes central virulence regulator PrfA. Microbiology 154, 3579–3589 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Ripio, M.-T., Dominguez-Bernal, G., Lara, M., Suarez, M. & Vazquez-Boland, J.-A. A Gly145Ser substitution in the transcriptional activator PrfA causes constitutive overexpression of virulence factors in Listeria monocytogenes. J. Bacteriol. 179, 1533–1540 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Shetron-Rama, L. M. et al. Isolation of Listeria monocytogenes mutants with high-level in vitro expression of host cytosol-induced gene products. Mol. Microbiol. 48, 1537–1551 (2003).

    Article  CAS  PubMed  Google Scholar 

  62. Vega, Y. et al. New Listeria monocytogenes prfA* mutants, transcriptional properties of PrfA* proteins and structure–function of the virulence regulator PrfA. Mol. Microbiol. 52, 1553–1565 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Wong, K. K. & Freitag, N. E. A novel mutation within the central Listeria monocytogenes regulator PrfA that results in constitutive expression of virulence gene products. J. Bacteriol. 186, 6265–6276 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Monk, I. R., Gahan, C. G. & Hill, C. Tools for functional postgenomic analysis of Listeria monocytogenes. Appl. Environ. Microbiol. 74, 3921–3934 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mauder, N. et al. Species-specific differences in the activity of PrfA, the key regulator of listerial virulence genes. J. Bacteriol. 188, 7941–7956 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Milohanic, E. et al. Transcriptome analysis of Listeria monocytogenes identifies three groups of genes differently regulated by PrfA. Mol. Microbiol. 47, 1613–1625 (2003).

    Article  CAS  PubMed  Google Scholar 

  67. Gray, M. J., Freitag, N. E. & Boor, K. J. How the bacterial pathogen Listeria monocytogenes mediates the switch from environmental Dr. Jekyll to pathogenic Mr. Hyde. Infect. Immun. 74, 2505–2512 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ollinger, J., Bowen, B., Wiedmann, M., Boor, K. J. & Bergholz, T. M. Listeria monocytogenes σB modulates PrfA-mediated virulence factor expression. Infect. Immun. 77, 2113–2124 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ollinger, J., Wiedmann, M. & Boor, K. J. σB- and PrfA-dependent transcription of genes previously classified as putative constituents of the Listeria monocytogenes PrfA regulon. Foodborne Pathog. Dis. 5, 281–293 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Toledo-Arana, A. et al. The Listeria transcriptional landscape from saprophytism to virulence. Nature 459, 950–956 (2009).

    Article  CAS  PubMed  Google Scholar 

  71. Mueller, K. J. & Freitag, N. E. Pleiotropic enhancement of bacterial pathogenesis resulting from the constitutive activation of the Listeria monocytogenes regulatory factor PrfA. Infect. Immun. 73, 1917–1926 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ripio, M. T. et al. Transcriptional activation of virulence genes in wild-type strains of Listeria monocytogenes in response to a change in the extracellular medium composition. Res. Microbiol. 147, 371–384 (1996).

    Article  CAS  PubMed  Google Scholar 

  73. Marr, A. K. et al. Overexpression of PrfA leads to growth inhibition of Listeria monocytogenes in glucose-containing culture media by interfering with glucose uptake. J. Bacteriol. 188, 3887–3901 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Brockstedt, D. G. & Dubensky, T. W. Promises and challenges for the development of Listeria monocytogenes-based immunotherapies. Expert Rev. Vaccines 7, 1069–1084 (2008).

    Article  PubMed  Google Scholar 

  75. Schoen, C. et al. Listeria monocytogenes as novel carrier system for the development of live vaccines. Int. J. Med. Microbiol. 298, 45–58 (2008).

    Article  CAS  PubMed  Google Scholar 

  76. Shen, H. et al. Recombinant Listeria monocytogenes as a live vaccine vehicle for the induction of protective anti-viral cell-mediated immunity. Proc. Natl Acad. Sci. USA 92, 3987–3991 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wood, L. M., Guirnalda, P. D., Seavey, M. M. & Paterson, Y. Cancer immunotherapy using Listeria monocytogenes and listerial virulence factors. Immunol. Res. 42, 233–245 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Bruhn, K. W., Craft, N. & Miller, J. F. Listeria as a vaccine vector. Microbes Infect. 9, 1226–1235 (2007).

    Article  CAS  PubMed  Google Scholar 

  79. Lauer, P. et al. Constitutive activation of the PrfA regulon enhances the potency of vaccines based on live-attenuated and killed but metabolically active Listeria monocytogenes strains. Infect. Immun. 76, 3742–3753 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Yan, L. et al. Selected prfA* mutations in recombinant attenuated Listeria monocytogenes strains augment expression of foreign immunogens and enhance vaccine-elicited humoral and cellular immune responses. Infect. Immun. 76, 3439–3450 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Tilney, L. G. & Portnoy, D. A. Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J. Cell Biol. 109, 1597–1608 (1989).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors acknowledge members of the Freitag laboratory for helpful discussions. The authors were supported by Public Health Service grants AI41816 (N.E.F.) from the National Institute of Allergy and Infectious Diseases (NIAID), by a NIAID Bacterial Pathogenesis training grant fellowship AI55396 (M.D.M.) and by a National Science Foundation Graduate Research Fellowship (G.C.P.). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the funding sources.

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Authors and Affiliations

  1. Nancy E. Freitag is at the Department of Microbiology and Immunology (MC790), University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, Illinois 606127344, USA.,

    Nancy E. Freitag

  2. Gary C. Port is at the Department of Molecular Microbiology, Washington University, St Louis, Missouri 63110, USA.,

    Gary C. Port

  3. Maurine D. Miner is at the Seattle Biomedical Research Institute, Seattle, Washington 98109–5219, USA.,

    Maurine D. Miner

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Freitag, N., Port, G. & Miner, M. Listeria monocytogenes — from saprophyte to intracellular pathogen. Nat Rev Microbiol 7, 623–628 (2009). https://doi.org/10.1038/nrmicro2171

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