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.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.036129-0
2010-05-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/156/5/1372.html?itemId=/content/journal/micro/10.1099/mic.0.036129-0&mimeType=html&fmt=ahah

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
    [Google Scholar]
  3. Archer G. L. 1998; Staphylococcus aureus: a well-armed pathogen. Clin Infect Dis 26:1179–1181
    [Google Scholar]
  4. Balibar C. J., Shen X., Tao J. 2009; The mevalonate pathway of Staphylococcus aureus. J Bacteriol 191:851–861
    [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
    [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
    [Google Scholar]
  9. Fischer W. 1994; Lipoteichoic acid and lipids in the membrane of Staphylococcus aureus. Med Microbiol Immunol 183:61–76
    [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
    [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
    [Google Scholar]
  14. Horsburgh M. J., Aish J. L., White I. J., Shaw L., Lithgow J. K., Foster S. J. 2002; σB modulates virulence determinant expression and stress resistance: characterization of a functional rsbU strain derived from Staphylococcus aureus 8325-4. J Bacteriol 184:5457–5467
    [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
    [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
    [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
    [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
    [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
    [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
    [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 17601475–1481
    [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
    [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
    [Google Scholar]
  27. Oshida T., Tomasz A. 1992; Isolation and characterization of a Tn 551-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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.036129-0
Loading
/content/journal/micro/10.1099/mic.0.036129-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

PDF

Supplementary material 3

PDF
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