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.

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2005-05-01
2020-07-15
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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]
    [Google Scholar]
  2. Anagnostopoulos C., Spizizen J. 1961; Requirements for transformation of Bacillus subtilis. J Bacteriol81:741–746
    [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 Lett220:155–160[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 Biochem237:575–583[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. Science286:2361–2364[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 Microbiol30:317–327[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 Bacteriol184:6123–6129[CrossRef]
    [Google Scholar]
  8. Cao M., Helmann J. D. 2004; The Bacillus subtilis extracytoplasmic-function σX factor regulates modification of the cell envelope and resistance to cationic antimicrobial peptides. J Bacteriol186:1136–1146[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 Biol316:443–457[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 Microbiol45:1267–1276[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 Biol3:543–550[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 Biochem240:352–357[CrossRef]
    [Google Scholar]
  13. Helmann J. D. 2002; The extracytoplasmic function (ECF) sigma factors. Adv Microb Physiol46:47–110
    [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. Biochemistry42:6545–6558[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 Microbiol32:41–50[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 Biol279:165–173[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 Bacteriol180:3765–3770
    [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 Microbiol31:361–371[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 Chem273:3718–3724[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 Biotechnol4:503–513
    [Google Scholar]
  21. Kunst F., Ogasawara N., Moszer I.. 148 other authors 1997; The complete genome sequence of the gram-positive bacterium Bacillus subtilis. Nature390:249–256[CrossRef]
    [Google Scholar]
  22. Lehrer R. I., Ganz T. 2002; Defensins of vertebrate animals. Curr Opin Immunol14:96–102[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 Microbiol50:1591–1604[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 Chemother48:2888–2896[CrossRef]
    [Google Scholar]
  25. Ogura M., Tanaka T. 2002; Recent progress in Bacillus subtilis two-component regulation. Front Biosci7: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 Bacteriol185:51–59[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 Microbiol49:1135–1144[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 J341:501–513[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. Microbiology150:2609–2617[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 Chem270:15598–15606[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 Chem274:8405–8410[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 Microbiol16:969–976[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 Microbiol52:1091–1105[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 Bacteriol185:3491–3498[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 Chemother42:2206–2214
    [Google Scholar]
  36. Vaara M., Vaara T. 1983; Polycations as outer membrane-disorganizing agents. Antimicrob Agents Chemother24:114–122[CrossRef]
    [Google Scholar]
  37. Vagner V., Dervyn E., Ehrlich S. D. 1998; A vector for systematic gene inactivation in Bacillus subtilis. Microbiology144:3097–3104[CrossRef]
    [Google Scholar]
  38. Wiegert T., Homuth G., Versteeg S., Schumann W. 2001; Alkaline shock induces the Bacillus subtilis sigma (W) regulon. Mol Microbiol41:59–71[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 J79:2002–2009[CrossRef]
    [Google Scholar]
  40. Yeaman M. R., Yount N. Y. 2003; Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev55:27–55[CrossRef]
    [Google Scholar]
  41. Zasloff M. 2002; Antimicrobial peptides of multicellular organisms. Nature415:389–395[CrossRef]
    [Google Scholar]
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