1887

Abstract

Stress responses of to membrane-active cationic antimicrobial peptides were studied. Global analysis of gene expression by DNA macroarray showed that peptides at a subinhibitory concentration activated numerous genes. A prominent pattern was the activation of two extracytoplasmic function sigma factor regulons, SigW and SigM. Two natural antimicrobial peptides, LL-37 and PG-1, were weak activators of SigW regulon genes, whereas their synthetic analogue poly--lysine was clearly a stronger activator of SigW. It was demonstrated for the first time that LL-37 is a strong and specific activator of the YxdJK two-component systems, one of the three highly homologous two-component systems sensing antimicrobial compounds. YxdJK regulates the expression of the YxdLM ABC transporter. The LiaRS (YvqCE) TCS was also strongly activated by LL-37, but its activation is not LL-37 specific, as was demonstrated by its activation with PG-1 and Triton X-100. Other strongly LL-37-induced genes included and . Taken together, the responses to cationic antimicrobial peptides revealed highly complex regulatory patterns and induction of several signal transduction pathways. The results suggest significant overlap between different stress regulons and interdependence of signal transduction pathways mediating stress responses.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.27761-0
2005-05-01
2019-11-16
Loading full text...

Full text loading...

/deliver/fulltext/micro/151/5/mic1511577.html?itemId=/content/journal/micro/10.1099/mic.0.27761-0&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 Microbiol 43, 1–14.[CrossRef]
    [Google Scholar]
  2. Anagnostopoulos, C. & Spizizen, J. ( 1961; ). Requirements for transformation of Bacillus subtilis. J Bacteriol 81, 741–746.
    [Google Scholar]
  3. Asai, K., Yamaguchi, H., Kang, C. M., Yoshida, K., Fujita, Y. & Sadaie, Y. ( 2003; ). DNA microarray analysis of Bacillus subtilis sigma factors of extracytoplasmic function family. FEMS Microbiol Lett 220, 155–160.[CrossRef]
    [Google Scholar]
  4. Aumelas, A., Mangoni, M., Roumestand, C., Chiche, L., Despaux, E., Grassy, G., Calas, B. & Chavanieu, A. ( 1996; ). Synthesis and solution structure of the antimicrobial peptide protegrin-1. Eur J Biochem 237, 575–583.[CrossRef]
    [Google Scholar]
  5. Breukink, E., Wiedemann, I., van Kraaij, C., Kuipers, O. P., Sahl, H. & de Kruijff, B. ( 1999; ). Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science 286, 2361–2364.[CrossRef]
    [Google Scholar]
  6. Brotz, H., Josten, M., Wiedemann, I., Schneider, U., Gotz, F., Bierbaum, G. & Sahl, H. G. ( 1998; ). Role of lipid-bound peptidoglycan precursors in the formation of pores by nisin, epidermin and other lantibiotics. Mol Microbiol 30, 317–327.[CrossRef]
    [Google Scholar]
  7. Cao, M. & Helmann, J. D. ( 2002; ). Regulation of the Bacillus subtilis bcrC bacitracin resistance gene by two extracytoplasmic function sigma factors. J Bacteriol 184, 6123–6129.[CrossRef]
    [Google Scholar]
  8. Cao, M. & Helmann, J. D. ( 2004; ). The Bacillus subtilis extracytoplasmic-function σ X factor regulates modification of the cell envelope and resistance to cationic antimicrobial peptides. J Bacteriol 186, 1136–1146.[CrossRef]
    [Google Scholar]
  9. Cao, M., Kobel, P. A., Morshedi, M. M., Wu, M. F., Paddon, C. & Helmann, J. D. ( 2002a; ). Defining the Bacillus subtilis sigma (W) regulon: a comparative analysis of promoter consensus search, run-off transcription/macroarray analysis (ROMA), and transcriptional profiling approaches. J Mol Biol 316, 443–457.[CrossRef]
    [Google Scholar]
  10. Cao, M., Wang, T., Ye, R. & Helmann, J. D. ( 2002b; ). Antibiotics that inhibit cell wall biosynthesis induce expression of the Bacillus subtilis sigma (W) and sigma (M) regulons. Mol Microbiol 45, 1267–1276.[CrossRef]
    [Google Scholar]
  11. Fahrner, R. L., Dieckmann, T., Harwig, S. S., Lehrer, R. I., Eisenberg, D. & Feigon, J. ( 1996; ). Solution structure of protegrin-1, a broad-spectrum antimicrobial peptide from porcine leukocytes. Chem Biol 3, 543–550.[CrossRef]
    [Google Scholar]
  12. Harwig, S. S., Waring, A., Yang, H. J., Cho, Y., Tan, L. & Lehrer, R. I. ( 1996; ). Intramolecular disulfide bonds enhance the antimicrobial and lytic activities of protegrins at physiological sodium chloride concentrations. Eur J Biochem 240, 352–357.[CrossRef]
    [Google Scholar]
  13. Helmann, J. D. ( 2002; ). The extracytoplasmic function (ECF) sigma factors. Adv Microb Physiol 46, 47–110.
    [Google Scholar]
  14. Henzler Wildman, K. A., Lee, D. K. & Ramamoorthy, A. ( 2003; ). Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37. Biochemistry 42, 6545–6558.[CrossRef]
    [Google Scholar]
  15. Horsburgh, M. J. & Moir, A. ( 1999; ). Sigma M, an ECF RNA polymerase sigma factor of Bacillus subtilis 168, is essential for growth and survival in high concentrations of salt. Mol Microbiol 32, 41–50.[CrossRef]
    [Google Scholar]
  16. Huang, X. & Helmann, J. D. ( 1998; ). Identification of target promoters for the Bacillus subtilis sigma X factor using a consensus-directed search. J Mol Biol 279, 165–173.[CrossRef]
    [Google Scholar]
  17. Huang, X., Fredrick, K. L. & Helmann, J. D. ( 1998; ). Promoter recognition by Bacillus subtilis sigma W: autoregulation and partial overlap with the sigma X regulon. J Bacteriol 180, 3765–3770.
    [Google Scholar]
  18. Huang, X., Gaballa, A., Cao, M. & Helmann, J. D. ( 1999; ). Identification of target promoters for the Bacillus subtilis extracytoplasmic function sigma factor, sigma W. Mol Microbiol 31, 361–371.[CrossRef]
    [Google Scholar]
  19. Johansson, J., Gudmundsson, G. H., Rottenberg, M. E., Berndt, K. D. & Agerberth, B. ( 1998; ). Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. J Biol Chem 273, 3718–3724.[CrossRef]
    [Google Scholar]
  20. Joseph, P., Fichant, G., Quentin, Y. & Denizot, F. ( 2002; ). Regulatory relationship of two-component and ABC transporter systems and clustering of their genes in the Bacillus/Clostridium group, suggest a functional link between them. J Mol Microbiol Biotechnol 4, 503–513.
    [Google Scholar]
  21. Kunst, F., Ogasawara, N., Moszer, I. & 148 other authors ( 1997; ). The complete genome sequence of the gram-positive bacterium Bacillus subtilis. Nature 390, 249–256.[CrossRef]
    [Google Scholar]
  22. Lehrer, R. I. & Ganz, T. ( 2002; ). Defensins of vertebrate animals. Curr Opin Immunol 14, 96–102.[CrossRef]
    [Google Scholar]
  23. 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 Microbiol 50, 1591–1604.[CrossRef]
    [Google Scholar]
  24. Mascher, T., Zimmer, S. L., Smith, T. A. & Helmann, J. D. ( 2004; ). Antibiotic-inducible promoter regulated by the cell envelope stress-sensing two-component system LiaRS of Bacillus subtilis. Antimicrob Agents Chemother 48, 2888–2896.[CrossRef]
    [Google Scholar]
  25. Ogura, M. & Tanaka, T. ( 2002; ). Recent progress in Bacillus subtilis two-component regulation. Front Biosci 7, d1815–d1824.[CrossRef]
    [Google Scholar]
  26. Ohki, R., Tateno, K., Okada, Y., Okajima, H., Asai, K., Sadaie, Y., Murata, M. & Aiso, T. ( 2003a; ). A bacitracin-resistant Bacillus subtilis gene encodes a homologue of the membrane-spanning subunit of the Bacillus licheniformis ABC transporter. J Bacteriol 185, 51–59.[CrossRef]
    [Google Scholar]
  27. Ohki, R., Giyanto, Tateno, K., Masuyama, W., Moriya, S., Kobayashi, K. & Ogasawara, N. ( 2003b; ). The BceRS two-component regulatory system induces expression of the bacitracin transporter, BceAB, in Bacillus subtilis. Mol Microbiol 49, 1135–1144.[CrossRef]
    [Google Scholar]
  28. Oren, Z., Lerman, J. C., Gudmundsson, G. H., Agerberth, B. & Shai, Y. ( 1999; ). Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem J 341, 501–513.[CrossRef]
    [Google Scholar]
  29. Pascale, J., Guiseppi, A., Sorokin, A. & Denizot, F. ( 2004; ). Characterization of the Bacillus subtilis YxdJ response regulator as the inducer of expression for the cognate ABC transporter YxdLM. Microbiology 150, 2609–2617.[CrossRef]
    [Google Scholar]
  30. Perego, M., Glaser, P., Minutello, A., Strauch, M. A., Leopold, K. & Fischer, W. ( 1995; ). Incorporation of d-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification of genes and regulation. J Biol Chem 270, 15598–15606.[CrossRef]
    [Google Scholar]
  31. Peschel, A., Otto, M., Jack, R. W., Kalbacher, H., Jung, G. & Götz, F. ( 1999; ). Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins and other antimicrobial peptides. J Biol Chem 274, 8405–8410.[CrossRef]
    [Google Scholar]
  32. Podlesek, Z., Comino, A., Herzog-Velikonja, B., Zgur-Bertok, D., Komel, R. & Grabnar, M. ( 1995; ). Bacillus licheniformis bacitracin-resistance ABC transporter: relationship to mammalian multidrug resistance. Mol Microbiol 16, 969–976.[CrossRef]
    [Google Scholar]
  33. Schobel, S., Zellmeier, S., Schumann, W. & Wiegert, T. ( 2004; ). The Bacillus subtilis sigmaW anti-sigma factor RsiW is degraded by intramembrane proteolysis through YluC. Mol Microbiol 52, 1091–1105.[CrossRef]
    [Google Scholar]
  34. Thackray, P. D. & Moir, A. ( 2003; ). SigM, an extracytoplasmic function sigma factor of Bacillus subtilis, is activated in response to cell wall antibiotics, ethanol, heat, acid, and superoxide stress. J Bacteriol 185, 3491–3498.[CrossRef]
    [Google Scholar]
  35. Turner, J., Cho, Y., Dinh, N. N., Waring, A. J. & Lehrer, R. I. ( 1998; ). Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 42, 2206–2214.
    [Google Scholar]
  36. Vaara, M. & Vaara, T. ( 1983; ). Polycations as outer membrane-disorganizing agents. Antimicrob Agents Chemother 24, 114–122.[CrossRef]
    [Google Scholar]
  37. Vagner, V., Dervyn, E. & Ehrlich, S. D. ( 1998; ). A vector for systematic gene inactivation in Bacillus subtilis. Microbiology 144, 3097–3104.[CrossRef]
    [Google Scholar]
  38. Wiegert, T., Homuth, G., Versteeg, S. & Schumann, W. ( 2001; ). Alkaline shock induces the Bacillus subtilis sigma (W) regulon. Mol Microbiol 41, 59–71.[CrossRef]
    [Google Scholar]
  39. Yang, L., Weiss, T. M., Lehrer, R. I. & Huang, H. W. ( 2000; ). Crystallization of antimicrobial pores in membranes: magainin and protegrin. Biophys J 79, 2002–2009.[CrossRef]
    [Google Scholar]
  40. Yeaman, M. R. & Yount, N. Y. ( 2003; ). Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55, 27–55.[CrossRef]
    [Google Scholar]
  41. Zasloff, M. ( 2002; ). Antimicrobial peptides of multicellular organisms. Nature 415, 389–395.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.27761-0
Loading
/content/journal/micro/10.1099/mic.0.27761-0
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