1887

Abstract

The Gram-positive bacterium is widely distributed in the environment and capable of causing food-borne infections in susceptible individuals. In this study, we investigated the cell envelope stress response in . Whole-genome transcriptional profiling was performed to investigate the response upon exposure to the cell wall antibiotic cefuroxime. Differential expression (at least twofold) of 558 genes was observed, corresponding to 20 % of the genome. The majority of genes that were strongly induced by cefuroxime exposure have cell-envelope-related functions, including the operon and the gene encoding penicillin-binding protein PBPD2. A large overlap was observed between the cefuroxime stimulon and genes known to be induced in in blood and during intracellular infection, indicating that the cell envelope stress response is active at various stages of the infectious process. We analysed the roles of the two-component systems LisRK and CesRK in the cell envelope response, showing that activation of the most highly cefuroxime-induced genes was LisR- and CesR-dependent. In addition, multiple VirRS- and LiaSR-regulated genes were found to be induced in response to cefuroxime exposure. In total, 53 % of the genes upregulated at least fourfold by cefuroxime exposure are under positive control by one of the four two-component systems. Using genetic analyses, we showed that several genes of the cefuroxime stimulon contribute to the innate resistance of to cefuroxime and tolerance to other cell-envelope-perturbing conditions. Collectively, these findings demonstrate central roles for two-component systems in orchestrating the cell envelope stress response in .

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.055467-0
2012-04-01
2021-03-04
Loading full text...

Full text loading...

/deliver/fulltext/micro/158/4/963.html?itemId=/content/journal/micro/10.1099/mic.0.055467-0&mimeType=html&fmt=ahah

References

  1. Abachin E., Poyart C., Pellegrini E., Milohanic E., Fiedler F., Berche P., Trieu-Cuot P.. ( 2002;). Formation of d-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol Microbiol43:1–14 [CrossRef][PubMed]
    [Google Scholar]
  2. Bailey T. L., Elkan C.. ( 1994;). Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol2:28–36[PubMed]
    [Google Scholar]
  3. Begley M., Hill C., Ross R. P.. ( 2006;). Tolerance of Listeria monocytogenes to cell envelope-acting antimicrobial agents is dependent on SigB. Appl Environ Microbiol72:2231–2234 [CrossRef][PubMed]
    [Google Scholar]
  4. Bierne H., Cossart P.. ( 2007;). Listeria monocytogenes surface proteins: from genome predictions to function. Microbiol Mol Biol Rev71:377–397 [CrossRef][PubMed]
    [Google Scholar]
  5. Camejo A., Buchrieser C., Couvé E., Carvalho F., Reis O., Ferreira P., Sousa S., Cossart P., Cabanes D.. ( 2009;). In vivo transcriptional profiling of Listeria monocytogenes and mutagenesis identify new virulence factors involved in infection. PLoS Pathog5:e1000449 [CrossRef][PubMed]
    [Google Scholar]
  6. Cao M., Wang T., Ye R., Helmann J. D.. ( 2002;). Antibiotics that inhibit cell wall biosynthesis induce expression of the Bacillus subtilis σW and σM regulons. Mol Microbiol45:1267–1276 [CrossRef][PubMed]
    [Google Scholar]
  7. Chakraborty T., Leimeister-Wächter M., Domann E., Hartl M., Goebel W., Nichterlein T., Notermans S.. ( 1992;). Coordinate regulation of virulence genes in Listeria monocytogenes requires the product of the prfA gene. J Bacteriol174:568–574[PubMed]
    [Google Scholar]
  8. Chatterjee S. S., Hossain H., Otten S., Kuenne C., Kuchmina K., Machata S., Domann E., Chakraborty T., Hain T.. ( 2006;). Intracellular gene expression profile of Listeria monocytogenes. Infect Immun74:1323–1338 [CrossRef][PubMed]
    [Google Scholar]
  9. Christiansen J. K., Larsen M. H., Ingmer H., Søgaard-Andersen L., Kallipolitis B. H.. ( 2004;). The RNA-binding protein Hfq of Listeria monocytogenes: role in stress tolerance and virulence. J Bacteriol186:3355–3362 [CrossRef][PubMed]
    [Google Scholar]
  10. Comenge Y., Quintiliani R. Jr, Li L., Dubost L., Brouard J. P., Hugonnet J. E., Arthur M.. ( 2003;). The CroRS two-component regulatory system is required for intrinsic β-lactam resistance in Enterococcus faecalis. J Bacteriol185:7184–7192 [CrossRef][PubMed]
    [Google Scholar]
  11. Cotter P. D., Emerson N., Gahan C. G., Hill C.. ( 1999;). Identification and disruption of lisRK, a genetic locus encoding a two-component signal transduction system involved in stress tolerance and virulence in Listeria monocytogenes. J Bacteriol181:6840–6843[PubMed]
    [Google Scholar]
  12. Cotter P. D., Guinane C. M., Hill C.. ( 2002;). The LisRK signal transduction system determines the sensitivity of Listeria monocytogenes to nisin and cephalosporins. Antimicrob Agents Chemother46:2784–2790 [CrossRef][PubMed]
    [Google Scholar]
  13. de las Heras A., Cain R. J., Bielecka M. K., Vázquez-Boland J. A.. ( 2011;). Regulation of Listeria virulence: PrfA master and commander. Curr Opin Microbiol14:118–127 [CrossRef][PubMed]
    [Google Scholar]
  14. Falord M., Mäder U., Hiron A., Débarbouillé M., Msadek T.. ( 2011;). Investigation of the Staphylococcus aureus GraSR regulon reveals novel links to virulence, stress response and cell wall signal transduction pathways. PLoS ONE6:e21323 [CrossRef][PubMed]
    [Google Scholar]
  15. Fournier B., Hooper D. C.. ( 2000;). A new two-component regulatory system involved in adhesion, autolysis, and extracellular proteolytic activity of Staphylococcus aureus. J Bacteriol182:3955–3964 [CrossRef][PubMed]
    [Google Scholar]
  16. Fournier B., Klier A., Rapoport G.. ( 2001;). The two-component system ArlS-ArlR is a regulator of virulence gene expression in Staphylococcus aureus. Mol Microbiol41:247–261 [CrossRef][PubMed]
    [Google Scholar]
  17. Fritsch F., Mauder N., Williams T., Weiser J., Oberle M., Beier D.. ( 2011;). The cell envelope stress response mediated by the LiaFSRLm three-component system of Listeria monocytogenes is controlled via the phosphatase activity of the bifunctional histidine kinase LiaSLm. Microbiology157:373–386 [CrossRef][PubMed]
    [Google Scholar]
  18. Gardan R., Duché O., Leroy-Sétrin S., Labadie J.. European Listeria Genome Consortium ( 2003;). Role of ctc from Listeria monocytogenes in osmotolerance. Appl Environ Microbiol69:154–161 [CrossRef][PubMed]
    [Google Scholar]
  19. Glaser P., Frangeul L., Buchrieser C., Rusniok C., Amend A., Baquero F., Berche P., Bloecker H., Brandt P.. & other authors ( 2001;). Comparative genomics of Listeria species. Science294:849–852[PubMed]
    [Google Scholar]
  20. Gottschalk S., Bygebjerg-Hove I., Bonde M., Nielsen P. K., Nguyen T. H., Gravesen A., Kallipolitis B. H.. ( 2008;). The two-component system CesRK controls the transcriptional induction of cell envelope-related genes in Listeria monocytogenes in response to cell wall-acting antibiotics. J Bacteriol190:4772–4776 [CrossRef][PubMed]
    [Google Scholar]
  21. Hancock L. E., Perego M.. ( 2004;). Systematic inactivation and phenotypic characterization of two-component signal transduction systems of Enterococcus faecalis V583. J Bacteriol186:7951–7958 [CrossRef][PubMed]
    [Google Scholar]
  22. Hof H.. ( 2003;). Listeriosis: therapeutic options. FEMS Immunol Med Microbiol35:203–205 [CrossRef][PubMed]
    [Google Scholar]
  23. Hsiao A., Ideker T., Olefsky J. M., Subramaniam S.. ( 2005;). VAMPIRE microarray suite: a web-based platform for the interpretation of gene expression data. Nucleic Acids Res33:Web Server issueW627–W632 [CrossRef][PubMed]
    [Google Scholar]
  24. Jordan S., Hutchings M. I., Mascher T.. ( 2008;). Cell envelope stress response in Gram-positive bacteria. FEMS Microbiol Rev32:107–146 [CrossRef][PubMed]
    [Google Scholar]
  25. Joseph B., Przybilla K., Stühler C., Schauer K., Slaghuis J., Fuchs T. M., Goebel W.. ( 2006;). Identification of Listeria monocytogenes genes contributing to intracellular replication by expression profiling and mutant screening. J Bacteriol188:556–568 [CrossRef][PubMed]
    [Google Scholar]
  26. Kallipolitis B. H., Ingmer H.. ( 2001;). Listeria monocytogenes response regulators important for stress tolerance and pathogenesis. FEMS Microbiol Lett204:111–115 [CrossRef][PubMed]
    [Google Scholar]
  27. Kallipolitis B. H., Ingmer H., Gahan C. G., Hill C., Søgaard-Andersen L.. ( 2003;). CesRK, a two-component signal transduction system in Listeria monocytogenes, responds to the presence of cell wall-acting antibiotics and affects β-lactam resistance. Antimicrob Agents Chemother47:3421–3429 [CrossRef][PubMed]
    [Google Scholar]
  28. Korsak D., Markiewicz Z., Gutkind G. O., Ayala J. A.. ( 2010;). Identification of the full set of Listeria monocytogenes penicillin-binding proteins and characterization of PBPD2 (Lmo2812). BMC Microbiol10:239 [CrossRef][PubMed]
    [Google Scholar]
  29. Kuroda M., Kuroda H., Oshima T., Takeuchi F., Mori H., Hiramatsu K.. ( 2003;). Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus. Mol Microbiol49:807–821 [CrossRef][PubMed]
    [Google Scholar]
  30. Larkin M. A., Blackshields G., Brown N. P., Chenna R., McGettigan P. A., McWilliam H., Valentin F., Wallace I. M., Wilm A.. & other authors ( 2007;). clustal w and clustal_x version 2.0. Bioinformatics23:2947–2948 [CrossRef][PubMed]
    [Google Scholar]
  31. Liang X., Zheng L., Landwehr C., Lunsford D., Holmes D., Ji Y.. ( 2005;). Global regulation of gene expression by ArlRS, a two-component signal transduction regulatory system of Staphylococcus aureus. J Bacteriol187:5486–5492 [CrossRef][PubMed]
    [Google Scholar]
  32. Mandin P., Fsihi H., Dussurget O., Vergassola M., Milohanic E., Toledo-Arana A., Lasa I., Johansson J., Cossart P.. ( 2005;). VirR, a response regulator critical for Listeria monocytogenes virulence. Mol Microbiol57:1367–1380 [CrossRef][PubMed]
    [Google Scholar]
  33. Mascher T., Margulis N. G., Wang T., Ye R. W., Helmann J. D.. ( 2003;). Cell wall stress responses in Bacillus subtilis: the regulatory network of the bacitracin stimulon. Mol Microbiol50:1591–1604 [CrossRef][PubMed]
    [Google Scholar]
  34. Milohanic E., Glaser P., Coppée J. Y., Frangeul L., Vega Y., Vázquez-Boland J. A., Kunst F., Cossart P., Buchrieser C.. ( 2003;). Transcriptome analysis of Listeria monocytogenes identifies three groups of genes differently regulated by PrfA. Mol Microbiol47:1613–1625 [CrossRef][PubMed]
    [Google Scholar]
  35. Mols M., van Kranenburg R., van Melis C. C. J., Moezelaar R., Abee T.. ( 2010;). Analysis of acid-stressed Bacillus cereus reveals a major oxidative response and inactivation-associated radical formation. Environ Microbiol12:873–885 [CrossRef][PubMed]
    [Google Scholar]
  36. Nielsen J. S., Lei L. K., Ebersbach T., Olsen A. S., Klitgaard J. K., Valentin-Hansen P., Kallipolitis B. H.. ( 2010;). Defining a role for Hfq in Gram-positive bacteria: evidence for Hfq-dependent antisense regulation in Listeria monocytogenes. Nucleic Acids Res38:907–919 [CrossRef][PubMed]
    [Google Scholar]
  37. Parkinson J. S.. ( 1993;). Signal transduction schemes of bacteria. Cell73:857–871 [CrossRef][PubMed]
    [Google Scholar]
  38. Pfaffl M. W.. ( 2001;). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res29:e45 [CrossRef][PubMed]
    [Google Scholar]
  39. Pfaffl M. W., Horgan G. W., Dempfle L.. ( 2002;). Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res30:e36 [CrossRef][PubMed]
    [Google Scholar]
  40. Pietiäinen M., Gardemeister M., Mecklin M., Leskelä S., Sarvas M., Kontinen V. P.. ( 2005;). Cationic antimicrobial peptides elicit a complex stress response in Bacillus subtilis that involves ECF-type sigma factors and two-component signal transduction systems. Microbiology151:1577–1592 [CrossRef][PubMed]
    [Google Scholar]
  41. Pietiäinen M., François P., Hyyryläinen H. L., Tangomo M., Sass V., Sahl H. G., Schrenzel J., Kontinen V. P.. ( 2009;). Transcriptome analysis of the responses of Staphylococcus aureus to antimicrobial peptides and characterization of the roles of vraDE and vraSR in antimicrobial resistance. BMC Genomics10:429 [CrossRef][PubMed]
    [Google Scholar]
  42. Quillin S. J., Schwartz K. T., Leber J. H.. ( 2011;). The novel Listeria monocytogenes bile sensor BrtA controls expression of the cholic acid efflux pump MdrT. Mol Microbiol81:129–142 [CrossRef][PubMed]
    [Google Scholar]
  43. Sleator R. D., Hill C.. ( 2005;). A novel role for the LisRK two-component regulatory system in listerial osmotolerance. Clin Microbiol Infect11:599–601 [CrossRef][PubMed]
    [Google Scholar]
  44. Stack H. M., Sleator R. D., Bowers M., Hill C., Gahan C. G.. ( 2005;). Role for HtrA in stress induction and virulence potential in Listeria monocytogenes. Appl Environ Microbiol71:4241–4247 [CrossRef][PubMed]
    [Google Scholar]
  45. Temple M. E., Nahata M. C.. ( 2000;). Treatment of listeriosis. Ann Pharmacother34:656–661 [CrossRef][PubMed]
    [Google Scholar]
  46. Thedieck K., Hain T., Mohamed W., Tindall B. J., Nimtz M., Chakraborty T., Wehland J., Jänsch L.. ( 2006;). The MprF protein is required for lysinylation of phospholipids in listerial membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on Listeria monocytogenes. Mol Microbiol62:1325–1339 [CrossRef][PubMed]
    [Google Scholar]
  47. Toledo-Arana A., Dussurget O., Nikitas G., Sesto N., Guet-Revillet H., Balestrino D., Loh E., Gripenland J., Tiensuu T.. & other authors ( 2009;). The Listeria transcriptional landscape from saprophytism to virulence. Nature459:950–956 [CrossRef][PubMed]
    [Google Scholar]
  48. Utaida S., Dunman P. M., Macapagal D., Murphy E., Projan S. J., Singh V. K., Jayaswal R. K., Wilkinson B. J.. ( 2003;). Genome-wide transcriptional profiling of the response of Staphylococcus aureus to cell-wall-active antibiotics reveals a cell-wall-stress stimulon. Microbiology149:2719–2732 [CrossRef][PubMed]
    [Google Scholar]
  49. van der Veen S., Hain T., Wouters J. A., Hossain H., de Vos W. M., Abee T., Chakraborty T., Wells-Bennik M. H.. ( 2007;). The heat-shock response of Listeria monocytogenes comprises genes involved in heat shock, cell division, cell wall synthesis, and the SOS response. Microbiology153:3593–3607 [CrossRef][PubMed]
    [Google Scholar]
  50. van der Veen S., van Schalkwijk S., Molenaar D., de Vos W. M., Abee T., Wells-Bennik M. H.. ( 2010;). The SOS response of Listeria monocytogenes is involved in stress resistance and mutagenesis. Microbiology156:374–384 [CrossRef][PubMed]
    [Google Scholar]
  51. Vazquez-Boland J. A., Kocks C., Dramsi S., Ohayon H., Geoffroy C., Mengaud J., Cossart P.. ( 1992;). Nucleotide sequence of the lecithinase operon of Listeria monocytogenes and possible role of lecithinase in cell-to-cell spread. Infect Immun60:219–230[PubMed]
    [Google Scholar]
  52. Vázquez-Boland J. A., Kuhn M., Berche P., Chakraborty T., Domínguez-Bernal G., Goebel W., González-Zorn B., Wehland J., Kreft J.. ( 2001;). Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev14:584–640 [CrossRef][PubMed]
    [Google Scholar]
  53. Wecke T., Mascher T.. ( 2011;). Antibiotic research in the age of omics: from expression profiles to interspecies communication. J Antimicrob Chemother66:2689–2704 [CrossRef][PubMed]
    [Google Scholar]
  54. Wilson R. L., Brown L. L., Kirkwood-Watts D., Warren T. K., Lund S. A., King D. S., Jones K. F., Hruby D. E.. ( 2006;). Listeria monocytogenes 10403S HtrA is necessary for resistance to cellular stress and virulence. Infect Immun74:765–768 [CrossRef][PubMed]
    [Google Scholar]
  55. Wonderling L. D., Wilkinson B. J., Bayles D. O.. ( 2004;). The htrA (degP) gene of Listeria monocytogenes 10403S is essential for optimal growth under stress conditions. Appl Environ Microbiol70:1935–1943 [CrossRef][PubMed]
    [Google Scholar]
  56. Woodward J. J., Iavarone A. T., Portnoy D. A.. ( 2010;). c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science328:1703–1705 [CrossRef][PubMed]
    [Google Scholar]
  57. Zhang C., Nietfeldt J., Zhang M., Benson A. K.. ( 2005;). Functional consequences of genome evolution in Listeria monocytogenes: the lmo0423 and lmo0422 genes encode σC and LstR, a lineage II-specific heat shock system. J Bacteriol187:7243–7253 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.055467-0
Loading
/content/journal/micro/10.1099/mic.0.055467-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error