1887

Abstract

Transcriptional profiling data accumulated in recent years for the clinically relevant pathogen have established a cell wall stress stimulon, which comprises a coordinately regulated set of genes that are upregulated in response to blockage of cell wall biogenesis. In particular, the expression of (SA2343, N315 notation), which encodes a putative 63 amino acid polypeptide of unknown biological function, increases over 100-fold in response to cell wall inhibition. Herein, we seek to understand the biological role that this gene plays in was found to be robustly induced by all cell wall-targeting antibiotics tested – vancomycin, oxacillin, penicillin G, phosphomycin, imipenem, hymeglusin and bacitracin – but not by antibiotics with other mechanisms of action, including ciprofloxacin, erythromycin, chloramphenicol, triclosan, rifampicin, novobiocin and carbonyl cyanide 3-chlorophenylhydrazone. Although a Δ strain had no appreciable shift in MICs for cell wall-targeting antibiotics, the knockout was shown to have reduced cell wall integrity in a variety of other assays. Additionally, the gene was shown to be important for virulence in a mouse sepsis model of infection.

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2010-05-01
2019-10-14
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References

  1. Amako, K., Umeda, A. & Murata, K. ( 1982; ). Arrangement of peptidoglycan in the cell wall of Staphylococcus spp. J Bacteriol 150, 844–850.
    [Google Scholar]
  2. Antignac, A., Sieradzki, K. & Tomasz, A. ( 2007; ). Perturbation of cell wall synthesis suppresses autolysis in Staphylococcus aureus: evidence for coregulation of cell wall synthetic and hydrolytic enzymes. J Bacteriol 189, 7573–7580.[CrossRef]
    [Google Scholar]
  3. Archer, G. L. ( 1998; ). Staphylococcus aureus: a well-armed pathogen. Clin Infect Dis 26, 1179–1181.[CrossRef]
    [Google Scholar]
  4. Balibar, C. J., Shen, X. & Tao, J. ( 2009; ). The mevalonate pathway of Staphylococcus aureus. J Bacteriol 191, 851–861.[CrossRef]
    [Google Scholar]
  5. Bernsel, A., Viklund, H., Hennerdal, A. & Elofsson, A. ( 2009; ). TOPCONS: consensus prediction of membrane protein topology. Nucleic Acids Res 37, W465–W468.[CrossRef]
    [Google Scholar]
  6. Beveridge, T. J. ( 1981; ). Ultrastructure, chemistry, and function of the bacterial wall. Int Rev Cytol 72, 229–317.
    [Google Scholar]
  7. Clemans, D. L., Kolenbrander, P. E., Debabov, D. V., Zhang, Q., Lunsford, R. D., Sakone, H., Whittaker, C. J., Heaton, M. P. & Neuhaus, F. C. ( 1999; ). Insertional inactivation of genes responsible for the d-alanylation of lipoteichoic acid in Streptococcus gordonii DL1 (Challis) affects intrageneric coaggregations. Infect Immun 67, 2464–2474.
    [Google Scholar]
  8. Collins, L. V., Kristian, S. A., Weidenmaier, C., Faigle, M., Van Kessel, K. P., Van Strijp, J. A., Gotz, 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]
    [Google Scholar]
  9. Fischer, W. ( 1994; ). Lipoteichoic acid and lipids in the membrane of Staphylococcus aureus. Med Microbiol Immunol 183, 61–76.[CrossRef]
    [Google Scholar]
  10. Giesbrecht, P., Kersten, T., Maidhof, H. & Wecke, J. ( 1998; ). Staphylococcal cell wall: morphogenesis and fatal variations in the presence of penicillin. Microbiol Mol Biol Rev 62, 1371–1414.
    [Google Scholar]
  11. Gross, M., Cramton, S. E., Gotz, F. & Peschel, A. ( 2001; ). Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces. Infect Immun 69, 3423–3426.[CrossRef]
    [Google Scholar]
  12. Guzman, L. M., Belin, D., Carson, M. J. & Beckwith, J. ( 1995; ). Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol 177, 4121–4130.
    [Google Scholar]
  13. Herbert, S., Bera, A., Nerz, C., Kraus, D., Peschel, A., Goerke, C., Meehl, M., Cheung, A. & Gotz, F. ( 2007; ). Molecular basis of resistance to muramidase and cationic antimicrobial peptide activity of lysozyme in staphylococci. PLoS Pathog 3, e102 [CrossRef]
    [Google Scholar]
  14. Horsburgh, M. J., Aish, J. L., White, I. J., Shaw, L., Lithgow, J. K. & Foster, S. J. ( 2002; ). σ B modulates virulence determinant expression and stress resistance: characterization of a functional rsbU strain derived from Staphylococcus aureus 8325-4. J Bacteriol 184, 5457–5467.[CrossRef]
    [Google Scholar]
  15. Hughes, A. H., Hancock, I. C. & Baddiley, J. ( 1973; ). The function of teichoic acids in cation control in bacterial membranes. Biochem J 132, 83–93.
    [Google Scholar]
  16. Kadurugamuwa, J. L., Sin, L., Albert, E., Yu, J., Francis, K., DeBoer, M., Rubin, M., Bellinger-Kawahara, C., Parr, T. R., Jr & Contag, P. R. ( 2003; ). Direct continuous method for monitoring biofilm infection in a mouse model. Infect Immun 71, 882–890.[CrossRef]
    [Google Scholar]
  17. Klevens, R. M., Morrison, M. A., Fridkin, S. K., Reingold, A., Petit, S., Gershman, K., Ray, S., Harrison, L. H., Lynfield, R. & other authors ( 2006; ). Community-associated methicillin-resistant Staphylococcus aureus and healthcare risk factors. Emerg Infect Dis 12, 1991–1993.[CrossRef]
    [Google Scholar]
  18. Koprivnjak, T., Mlakar, V., Swanson, L., Fournier, B., Peschel, A. & Weiss, J. P. ( 2006; ). Cation-induced transcriptional regulation of the dlt operon of Staphylococcus aureus. J Bacteriol 188, 3622–3630.[CrossRef]
    [Google Scholar]
  19. 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 Microbiol 49, 807–821.
    [Google Scholar]
  20. Lamarche, M. G., Wanner, B. L., Crepin, S. & Harel, J. ( 2008; ). The phosphate regulon and bacterial virulence: a regulatory network connecting phosphate homeostasis and pathogenesis. FEMS Microbiol Rev 32, 461–473.[CrossRef]
    [Google Scholar]
  21. Lee, C. Y., Buranen, S. L. & Ye, Z. H. ( 1991; ). Construction of single-copy integration vectors for Staphylococcus aureus. Gene 103, 101–105.[CrossRef]
    [Google Scholar]
  22. McAleese, F., Wu, S. W., Sieradzki, K., Dunman, P., Murphy, E., Projan, S. & Tomasz, A. ( 2006; ). Overexpression of genes of the cell wall stimulon in clinical isolates of Staphylococcus aureus exhibiting vancomycin-intermediate- S. aureus-type resistance to vancomycin. J Bacteriol 188, 1120–1133.[CrossRef]
    [Google Scholar]
  23. McCallum, N., Spehar, G., Bischoff, M. & Berger-Bachi, B. ( 2006; ). Strain dependence of the cell wall-damage induced stimulon in Staphylococcus aureus. Biochim Biophys Acta 1760, 1475–1481.[CrossRef]
    [Google Scholar]
  24. Muthaiyan, A., Silverman, J. A., Jayaswal, R. K. & Wilkinson, B. J. ( 2008; ). Transcriptional profiling reveals that daptomycin induces the Staphylococcus aureus cell wall stress stimulon and genes responsive to membrane depolarization. Antimicrob Agents Chemother 52, 980–990.[CrossRef]
    [Google Scholar]
  25. Navarre, W. W. & Schneewind, O. ( 1999; ). Surface proteins of Gram-positive bacteria and mechanisms of their targeting to the cell wall envelope. Microbiol Mol Biol Rev 63, 174–229.
    [Google Scholar]
  26. Neuhaus, F. C., Heaton, M. P., Debabov, D. V. & Zhang, Q. ( 1996; ). The dlt operon in the biosynthesis of d-alanyl-lipoteichoic acid in Lactobacillus casei. Microb Drug Resist 2, 77–84.[CrossRef]
    [Google Scholar]
  27. Oshida, T. & Tomasz, A. ( 1992; ). Isolation and characterization of a Tn551-autolysis mutant of Staphylococcus aureus. J Bacteriol 174, 4952–4959.
    [Google Scholar]
  28. Peschel, A., Otto, M., Jack, R. W., Kalbacher, H., Jung, G. & Gotz, 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]
  29. Qoronfleh, M. W. & Wilkinson, B. J. ( 1986; ). Effects of growth of methicillin-resistant and -susceptible Staphylococcus aureus in the presence of beta-lactams on peptidoglycan structure and susceptibility to lytic enzymes. Antimicrob Agents Chemother 29, 250–257.[CrossRef]
    [Google Scholar]
  30. Ramadurai, L., Lockwood, K. J., Nadakavukaren, M. J. & Jayaswal, R. K. ( 1999; ). Characterization of a chromosomally encoded glycylglycine endopeptidase of Staphylococcus aureus. Microbiology 145, 801–808.[CrossRef]
    [Google Scholar]
  31. Sobral, R. G., Jones, A. E., Des Etages, S. G., Dougherty, T. J., Peitzsch, R. M., Gaasterland, T., Ludovice, A. M., de Lencastre, H. & Tomasz, A. ( 2007; ). Extensive and genome-wide changes in the transcription profile of Staphylococcus aureus induced by modulating the transcription of the cell wall synthesis gene murF. J Bacteriol 189, 2376–2391.[CrossRef]
    [Google Scholar]
  32. Stapleton, M. R., Horsburgh, M. J., Hayhurst, E. J., Wright, L., Jonsson, I. M., Tarkowski, A., Kokai-Kun, J. F., Mond, J. J. & Foster, S. J. ( 2007; ). Characterization of IsaA and SceD, two putative lytic transglycosylases of Staphylococcus aureus. J Bacteriol 189, 7316–7325.[CrossRef]
    [Google Scholar]
  33. Steidl, R., Pearson, S., Stephenson, R. E., Ledala, N., Sitthisak, S., Wilkinson, B. J. & Jayaswal, R. K. ( 2008; ). Staphylococcus aureus cell wall stress stimulon gene-lacZ fusion strains: potential for use in screening for cell wall-active antimicrobials. Antimicrob Agents Chemother 52, 2923–2925.[CrossRef]
    [Google Scholar]
  34. Tomasz, A., Moreillon, P. & Pozzi, G. ( 1988; ). Insertional inactivation of the major autolysin gene of Streptococcus pneumoniae. J Bacteriol 170, 5931–5934.
    [Google Scholar]
  35. 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. Microbiology 149, 2719–2732.[CrossRef]
    [Google Scholar]
  36. Wecke, J., Perego, M. & Fischer, W. ( 1996; ). d-Alanine deprivation of Bacillus subtilis teichoic acids is without effect on cell growth and morphology but affects the autolytic activity. Microb Drug Resist 2, 123–129.[CrossRef]
    [Google Scholar]
  37. Wilding, E. I., Brown, J. R., Bryant, A. P., Chalker, A. F., Holmes, D. J., Ingraham, K. A., Iordanescu, S., So, C. Y., Rosenberg, M. & Gwynn, M. N. ( 2000; ). Identification, evolution, and essentiality of the mevalonate pathway for isopentenyl diphosphate biosynthesis in Gram-positive cocci. J Bacteriol 182, 4319–4327.[CrossRef]
    [Google Scholar]
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