1887

Abstract

Bacterial cell surface charge is responsible for susceptibility to cationic antimicrobial peptides. Previously, and were identified as factors conferring a positive charge upon cell surfaces. In this study, we investigated the regulation of cell surface charge during growth. Using a group of MW2 mutants, which are gene-inactivated in 15 types of two-component systems (TCSs), we tested and expression and found that two TCSs, and , were associated with and expression in a growth phase-dependent manner. The first of these, , which had already been identified as a sensor of antimicrobial peptides and a positive regulator of and expression, was expressed strongly in the exponential phase, while its expression was significantly suppressed by in the stationary phase, resulting in higher expression of and in the exponential phase and lower expression in the stationary phase. Since both types of expression affected the cell surface charge, the susceptibility to antimicrobial peptides and cationic antibiotics was changed during growth. Furthermore, we found that the ability to sense antimicrobial peptides only functioned in the exponential phase. These results suggest that cell surface charge is tightly regulated during growth in .

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2011-06-01
2019-10-15
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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 Microbiol 43:, 1–14. [CrossRef].[PubMed].
    [Google Scholar]
  2. Baba T. , Takeuchi F. , Kuroda M. , Yuzawa H. , Aoki K. , Oguchi A. , Nagai Y. , Iwama N. , Asano K. , Naimi T. , Kuroda H. , Cui L. , Yamamoto K. , Hiramatsu K. . ( 2002; ). Genome and virulence determinants of high virulence community-acquired MRSA. . Lancet 359:, 1819–1827. [CrossRef].[PubMed].
    [Google Scholar]
  3. Braff M. H. , Jones A. L. , Skerrett S. J. , Rubens C. E. . ( 2007; ). Staphylococcus aureus exploits cathelicidin antimicrobial peptides produced during early pneumonia to promote staphylokinase-dependent fibrinolysis. . J Infect Dis 195:, 1365–1372. [CrossRef].[PubMed].
    [Google Scholar]
  4. Cheung A. L. , Bayer A. S. , Zhang G. , Gresham H. , Xiong Y. Q. . ( 2004; ). Regulation of virulence determinants in vitro and in vivo in Staphylococcus aureus . . FEMS Immunol Med Microbiol 40:, 1–9. [CrossRef].[PubMed].
    [Google Scholar]
  5. Collins L. V. , Kristian S. A. , Weidenmaier C. , Faigle M. , Van Kessel K. P. , Van Strijp J. A. , Götz F. , Neumeister B. , Peschel A. . ( 2002; ). Staphylococcus aureus strains lacking d-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice. . J Infect Dis 186:, 214–219. [CrossRef].[PubMed].
    [Google Scholar]
  6. Cunliffe R. N. . ( 2003; ). Alpha-defensins in the gastrointestinal tract. . Mol Immunol 40:, 463–467. [CrossRef].[PubMed].
    [Google Scholar]
  7. Deurenberg R. H. , Vink C. , Kalenic S. , Friedrich A. W. , Bruggeman C. A. , Stobberingh E. E. . ( 2007; ). The molecular evolution of methicillin-resistant Staphylococcus aureus . . Clin Microbiol Infect 13:, 222–235. [CrossRef].[PubMed].
    [Google Scholar]
  8. Fellermann K. , Wehkamp J. , Herrlinger K. R. , Stange E. F. . ( 2003; a). Crohn’s disease: a defensin deficiency syndrome?. Eur J Gastroenterol Hepatol 15:, 627–634. [CrossRef].[PubMed].
    [Google Scholar]
  9. Fellermann K. , Wehkamp J. , Stange E. F. . ( 2003; b). Antimicrobial peptides in the skin. . N Engl J Med 348:, 361–363, author reply 361–363. [CrossRef].[PubMed].
    [Google Scholar]
  10. Foster T. J. . ( 2004; ). The Staphylococcus aureus “superbug”. . J Clin Invest 114:, 1693–1696.[PubMed].[CrossRef]
    [Google Scholar]
  11. Foster T. J. . ( 2005; ). Immune evasion by staphylococci. . Nat Rev Microbiol 3:, 948–958. [CrossRef].[PubMed].
    [Google Scholar]
  12. Ganz T. , Lehrer R. I. . ( 1995; ). Defensins. . Pharmacol Ther 66:, 191–205. [CrossRef].[PubMed].
    [Google Scholar]
  13. Ganz T. , Selsted M. E. , Szklarek D. , Harwig S. S. , Daher K. , Bainton D. F. , Lehrer R. I. . ( 1985; ). Defensins. Natural peptide antibiotics of human neutrophils. . J Clin Invest 76:, 1427–1435. [CrossRef].[PubMed].
    [Google Scholar]
  14. Geisinger E. , Adhikari R. P. , Jin R. , Ross H. F. , Novick R. P. . ( 2006; ). Inhibition of rot translation by RNAIII, a key feature of agr function. . Mol Microbiol 61:, 1038–1048. [CrossRef].[PubMed].
    [Google Scholar]
  15. Gottenbos B. , Grijpma D. W. , van der Mei H. C. , Feijen J. , Busscher H. J. . ( 2001; ). Antimicrobial effects of positively charged surfaces on adhering Gram-positive and Gram-negative bacteria. . J Antimicrob Chemother 48:, 7–13. [CrossRef].[PubMed].
    [Google Scholar]
  16. Gross M. , Cramton S. E. , Götz F. , Peschel A. . ( 2001; ). Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces. . Infect Immun 69:, 3423–3426. [CrossRef].[PubMed].
    [Google Scholar]
  17. Grundmann H. , Aires-de-Sousa M. , Boyce J. , Tiemersma E. . ( 2006; ). Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat. . Lancet 368:, 874–885. [CrossRef].[PubMed].
    [Google Scholar]
  18. Howden B. P. , Stinear T. P. , Allen D. L. , Johnson P. D. , Ward P. B. , Davies J. K. . ( 2008; ). Genomic analysis reveals a point mutation in the two-component sensor gene graS that leads to intermediate vancomycin resistance in clinical Staphylococcus aureus . . Antimicrob Agents Chemother 52:, 3755–3762. [CrossRef].[PubMed].
    [Google Scholar]
  19. Huntzinger E. , Boisset S. , Saveanu C. , Benito Y. , Geissmann T. , Namane A. , Lina G. , Etienne J. , Ehresmann B. et al. ( 2005; ). Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression. . EMBO J 24:, 824–835. [CrossRef].[PubMed].
    [Google Scholar]
  20. Jin T. , Bokarewa M. , Foster T. , Mitchell J. , Higgins J. , Tarkowski A. . ( 2004; ). Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. . J Immunol 172:, 1169–1176.[PubMed].[CrossRef]
    [Google Scholar]
  21. Komatsuzawa H. , Ohta K. , Fujiwara T. , Choi G. H. , Labischinski H. , Sugai M. . ( 2001; ). Cloning and sequencing of the gene, fmtC, which affects oxacillin resistance in methicillin-resistant Staphylococcus aureus . . FEMS Microbiol Lett 203:, 49–54. [CrossRef].[PubMed].
    [Google Scholar]
  22. Komatsuzawa H. , Fujiwara T. , Nishi H. , Yamada S. , Ohara M. , McCallum N. , Berger-Bächi B. , Sugai M. . ( 2004; ). The gate controlling cell wall synthesis in Staphylococcus aureus . . Mol Microbiol 53:, 1221–1231. [CrossRef].[PubMed].
    [Google Scholar]
  23. Koprivnjak T. , Peschel A. , Gelb M. H. , Liang N. S. , Weiss J. P. . ( 2002; ). Role of charge properties of bacterial envelope in bactericidal action of human group IIA phospholipase A2 against Staphylococcus aureus . . J Biol Chem 277:, 47636–47644. [CrossRef].[PubMed].
    [Google Scholar]
  24. Kraus D. , Herbert S. , Kristian S. A. , Khosravi A. , Nizet V. , Götz F. , Peschel A. . ( 2008; ). The GraRS regulatory system controls Staphylococcus aureus susceptibility to antimicrobial host defenses. . BMC Microbiol 8:, 85. [CrossRef].[PubMed].
    [Google Scholar]
  25. Kreiswirth B. N. , Löfdahl S. , Betley M. J. , O‚Reilly M. , Schlievert P. M. , Bergdoll M. S. , Novick R. P. . ( 1983; ). The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. . Nature 305:, 709–712. [CrossRef].[PubMed].
    [Google Scholar]
  26. Kristian S. A. , Datta V. , Weidenmaier C. , Kansal R. , Fedtke I. , Peschel A. , Gallo R. L. , Nizet V. . ( 2005; ). d-Alanylation of teichoic acids promotes group A Streptococcus antimicrobial peptide resistance, neutrophil survival, and epithelial cell invasion. . J Bacteriol 187:, 6719–6725. [CrossRef].[PubMed].
    [Google Scholar]
  27. Larrick J. W. , Hirata M. , Balint R. F. , Lee J. , Zhong J. , Wright S. C. . ( 1995; ). Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. . Infect Immun 63:, 1291–1297.[PubMed].
    [Google Scholar]
  28. Lehrer R. I. , Ganz T. . ( 1999; ). Antimicrobial peptides in mammalian and insect host defence. . Curr Opin Immunol 11:, 23–27. [CrossRef].[PubMed].
    [Google Scholar]
  29. Li M. , Cha D. J. , Lai Y. , Villaruz A. E. , Sturdevant D. E. , Otto M. . ( 2007; a). The antimicrobial peptide-sensing system aps of Staphylococcus aureus . . Mol Microbiol 66:, 1136–1147. [CrossRef].[PubMed].
    [Google Scholar]
  30. Li M. , Lai Y. , Villaruz A. E. , Cha D. J. , Sturdevant D. E. , Otto M. . ( 2007; b). Gram-positive three-component antimicrobial peptide-sensing system. . Proc Natl Acad Sci U S A 104:, 9469–9474. [CrossRef].[PubMed].
    [Google Scholar]
  31. Lowy F. D. . ( 1998; ). Staphylococcus aureus infections. . N Engl J Med 339:, 520–532. [CrossRef].[PubMed].
    [Google Scholar]
  32. Luong T. T. , Lee C. Y. . ( 2006; ). The arl locus positively regulates Staphylococcus aureus type 5 capsule via an mgrA-dependent pathway. . Microbiology 152:, 3123–3131. [CrossRef].[PubMed].
    [Google Scholar]
  33. Manders S. M. . ( 1998; ). Toxin-mediated streptococcal and staphylococcal disease. . J Am Acad Dermatol 39:, 383–398, quiz 399–400. [CrossRef].[PubMed].
    [Google Scholar]
  34. Matsuo M. , Kato F. , Oogai Y. , Kawai T. , Sugai M. , Komatsuzawa H. . ( 2010; ). Distinct two-component systems in methicillin-resistant Staphylococcus aureus can change the susceptibility to antimicrobial agents. . J Antimicrob Chemother 65:, 1536–1537. [CrossRef].[PubMed].
    [Google Scholar]
  35. Meehl M. , Herbert S. , Götz F. , Cheung A. . ( 2007; ). Interaction of the GraRS two-component system with the VraFG ABC transporter to support vancomycin-intermediate resistance in Staphylococcus aureus . . Antimicrob Agents Chemother 51:, 2679–2689. [CrossRef].[PubMed].
    [Google Scholar]
  36. Midorikawa K. , Ouhara K. , Komatsuzawa H. , Kawai T. , Yamada S. , Fujiwara T. , Yamazaki K. , Sayama K. , Taubman M. A. et al. ( 2003; ). Staphylococcus aureus susceptibility to innate antimicrobial peptides, beta-defensins and CAP18, expressed by human keratinocytes. . Infect Immun 71:, 3730–3739. [CrossRef].[PubMed].
    [Google Scholar]
  37. Morfeldt E. , Taylor D. , von Gabain A. , Arvidson S. . ( 1995; ). Activation of alpha-toxin translation in Staphylococcus aureus by the trans-encoded antisense RNA, RNAIII. . EMBO J 14:, 4569–4577.[PubMed].
    [Google Scholar]
  38. Novick R. P. . ( 2003; ). Autoinduction and signal transduction in the regulation of staphylococcal virulence. . Mol Microbiol 48:, 1429–1449. [CrossRef].[PubMed].
    [Google Scholar]
  39. Novick R. P. , Geisinger E. . ( 2008; ). Quorum sensing in staphylococci. . Annu Rev Genet 42:, 541–564. [CrossRef].[PubMed].
    [Google Scholar]
  40. Ong P. Y. , Ohtake T. , Brandt C. , Strickland I. , Boguniewicz M. , Ganz T. , Gallo R. L. , Leung D. Y. . ( 2002; ). Endogenous antimicrobial peptides and skin infections in atopic dermatitis. . N Engl J Med 347:, 1151–1160. [CrossRef].[PubMed].
    [Google Scholar]
  41. Ouhara K. , Komatsuzawa H. , Kawai T. , Nishi H. , Fujiwara T. , Fujiue Y. , Kuwabara M. , Sayama K. , Hashimoto K. , Sugai M. . ( 2008; ). Increased resistance to cationic antimicrobial peptide LL-37 in methicillin-resistant strains of Staphylococcus aureus . . J Antimicrob Chemother 61:, 1266–1269. [CrossRef].[PubMed].
    [Google Scholar]
  42. 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].[PubMed].
    [Google Scholar]
  43. Peschel A. , Jack R. W. , Otto M. , Collins L. V. , Staubitz P. , Nicholson G. , Kalbacher H. , Nieuwenhuizen W. F. , Jung G. et al. ( 2001; ). Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. . J Exp Med 193:, 1067–1076. [CrossRef].[PubMed].
    [Google Scholar]
  44. Poyart C. , Pellegrini E. , Marceau M. , Baptista M. , Jaubert F. , Lamy M. C. , Trieu-Cuot P. . ( 2003; ). Attenuated virulence of Streptococcus agalactiae deficient in d-alanyl-lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells. . Mol Microbiol 49:, 1615–1625. [CrossRef].[PubMed].
    [Google Scholar]
  45. Pütsep K. , Carlsson G. , Boman H. G. , Andersson M. . ( 2002; ). Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. . Lancet 360:, 1144–1149. [CrossRef].[PubMed].
    [Google Scholar]
  46. Ramanathan B. , Davis E. G. , Ross C. R. , Blecha F. . ( 2002; ). Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. . Microbes Infect 4:, 361–372. [CrossRef].[PubMed].
    [Google Scholar]
  47. Rooijakkers S. H. , van Kessel K. P. , van Strijp J. A. . ( 2005; ). Staphylococcal innate immune evasion. . Trends Microbiol 13:, 596–601. [CrossRef].[PubMed].
    [Google Scholar]
  48. Sau S. , Sun J. , Lee C. Y. . ( 1997; ). Molecular characterization and transcriptional analysis of type 8 capsule genes in Staphylococcus aureus . . J Bacteriol 179:, 1614–1621. [CrossRef].[PubMed].
    [Google Scholar]
  49. Selsted M. E. , Ouellette A. J. . ( 2005; ). Mammalian defensins in the antimicrobial immune response. . Nat Immunol 6:, 551–557. [CrossRef].[PubMed].
    [Google Scholar]
  50. Sieprawska-Lupa M. , Mydel P. , Krawczyk K. , Wójcik K. , Puklo M. , Lupa B. , Suder P. , Silberring J. , Reed M. et al. ( 2004; ). Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. . Antimicrob Agents Chemother 48:, 4673–4679. [CrossRef].[PubMed].
    [Google Scholar]
  51. Wehkamp J. , Fellermann K. , Herrlinger K. R. , Baxmann S. , Schmidt K. , Schwind B. , Duchrow M. , Wohlschläger C. , Feller A. C. , Stange E. F. . ( 2002; ). Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease. . Eur J Gastroenterol Hepatol 14:, 745–752. [CrossRef].[PubMed].
    [Google Scholar]
  52. Yang S. J. , Xiong Y. Q. , Dunman P. M. , Schrenzel J. , François P. , Peschel A. , Bayer A. S. . ( 2009; a). Regulation of mprF in daptomycin-nonsusceptible Staphylococcus aureus strains. . Antimicrob Agents Chemother 53:, 2636–2637. [CrossRef].[PubMed].
    [Google Scholar]
  53. Yang S. J. , Kreiswirth B. N. , Sakoulas G. , Yeaman M. R. , Xiong Y. Q. , Sawa A. , Bayer A. S. . ( 2009; b). Enhanced expression of dltABCD is associated with the development of daptomycin nonsusceptibility in a clinical endocarditis isolate of Staphylococcus aureus . . J Infect Dis 200:, 1916–1920. [CrossRef].[PubMed].
    [Google Scholar]
  54. Zaiou M. , Gallo R. L. . ( 2002; ). Cathelicidins, essential gene-encoded mammalian antibiotics. . J Mol Med 80:, 549–561. [CrossRef].[PubMed].
    [Google Scholar]
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