Skip to main content

Advertisement

SpringerLink
Log in

Thickening of the cell wall in macrolide-resistant Staphylococcus aureus

  • Original Paper
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

Macrolides are widely used at low dosage for long-term therapy of chronic sinusitis. Twenty clinical macrolide-resistant Staphylococcus aureus strains were morphologically compared with 10 clinical macrolide-sensitive strains. PCR amplification was performed to determine the presence of four known macrolide resistance genes. Transmission electron microscopy revealed significantly thicker cell walls in clinical macrolide-resistant strains. Even though the ultrastructural characteristics were shared by all macrolide-resistant strains, they were not associated with the presence or absence of the known macrolide-resistance genes. We also demonstrated that macrolide-resistant mutant strains derived in vitro from a macrolide-sensitive parent strain had thickened cell walls and did not harbor the known macrolide-resistance genes. These results, therefore, revealed that macrolide-resistant S. aureus strains have thickened cell walls as a common ultrastructural characteristic and that cell wall thickening is likely mediated by an unknown gene which is unrelated to any known macrolide resistance gene.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Mölstad S, Erntell M, Hanberger H, Melander E, Norman C, Skoog G, Lundborg CS, Söderström A, Torell E, Cars O (2008) Sustained reduction of antibiotic use and low bacterial resistance: 10-year follow-up of the Swedish Strama programme. Lancet Infect Dis 8:125–132

    Article  PubMed  Google Scholar 

  2. Hatipoğlu U, Rubinstein I (2008) Anti-inflammatory treatment of chronic rhinosinusitis: a shifting paradigm. Curr Allergy Asthma 8:154–161

    Article  Google Scholar 

  3. Wada T, Sata M, Sato J, Tokairin Y, Machiya J, Hirama N, Arao T, Inoue S, Takabatake N, Shibata Y, Kubota I (2007) Clarithromycin suppresses invasiveness of human lung adenocarcinoma cells. Chemotherapy 53:77–84

    Article  PubMed  CAS  Google Scholar 

  4. Wallwork B, Coman W, Mackay-Sim A, Greiff L, Cervin A (2006) A double blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis. Laryngoscope 116:189–193

    Article  PubMed  CAS  Google Scholar 

  5. Felmingham D (2007) Comparative antimicrobial susceptibility of respiratory tract pathogens. Chemotherapy 50(Suppl):3–10

    Google Scholar 

  6. Merino LA, Ronconi MC, Hreñuk GE, de Pepe MG (2003) Bacteriologic findings in patients with chronic sinusitis. Ear Nose Throat J 82:798–806

    PubMed  Google Scholar 

  7. Hyo Y, Yamada S, Harada T (2008) Characteristic cell wall ultrastructure of a macrolide-resistant Staphylococcus capitis strain isolated from a patient with chronic sinusitis. Med Mol Morphol 41:160–164

    Article  PubMed  Google Scholar 

  8. Yamada S, Sugai M, Komatsuzawa H, Nakashima S, Oshida T, Matsumoto A, Suginaka H (1996) An autolysin ring associated with cell separation of Staphylococcus aureus. J Bacteriol 178:1565–1571

    PubMed  CAS  PubMed Central  Google Scholar 

  9. Nagayama A, Yamaguchi K, Watanabe K, Tanaka M, Kobayashi I, Nagasawa Z (2008) Final report from the Committee on Antimicrobial Susceptibility Testing, Japanese Society of Chemotherapy, on the agar dilution method. J Infect Chemother 14:383–392

    Article  PubMed  CAS  Google Scholar 

  10. Leclercq R (2002) Mechanisms of resistance to macrolides and lincosamides; nature of resistance elements and their clinical implication. Clin Infect Dis 34:482–492

    Article  PubMed  CAS  Google Scholar 

  11. Martineau F, Picard FJ, Lansac N, Ménard C, Roy PH, Ouellette M, Bergeron MG (2000) Correlation between the resistance genotype determined by multiplex PCR assays and the antibiotics susceptibility patterns of Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother 44:231–238

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Janosi L, Nakajima Y, Hashimoto H (1990) Characterization of plasmids that confer inducible resistance to 14-membered macrolides and streptogramin type B antibiotics in Staphylococcus aureus. Microbiol Immunol 34:723–735

    Article  PubMed  CAS  Google Scholar 

  13. Sugai M, Yamada S, Nakashima S, Komatsuzawa H, Matsumoto A, Oshida T, Suginaka H (1997) Localized perforation of the cell wall by a major autolysin: atl gene products and the onset of penicillin-induced lysis of Staphylococcus aureus. J Bacteriol 179:2958–2962

    PubMed  CAS  PubMed Central  Google Scholar 

  14. Yamada S, Matsumoto A (1984) Localization of protein A on the cell surface of Staphylococcus aureus Cowan I and protein A-deficient strains. J Electron Microsc 33:172–174

    CAS  Google Scholar 

  15. Yamada S, Hyo Y, Ohmori S, Ohuchi M (2007) Role of ciprofloxacin in its synergistic effect with fosfomycin on drug-resistant strains of Pseudomonas aeruginosa. Chemotherapy 53:202–209

    Article  PubMed  CAS  Google Scholar 

  16. Hyo Y, Yamada S, Harada T (2012) Antimicrobial effects of Burow’s solution on Staphylococcus aureus and Pseudomonas aeruginosa. Med Mol Morphol 45:66–71

    Article  PubMed  Google Scholar 

  17. Fukutsuji K, Yamada S, Harada T (2013) Ultrastructural cell wall characteristics of gentamycin-resistant Staphylococcus aureus isolate. Med Mol Morphol (in press)

  18. Cui L, Ma X, Sato K, Okuma K, Tenover FC, Mamizuka EM, Gemmell CG, Kim MN, Ploy MC, El-Solh N, Ferraz V, Hiramatsu K (2003) Cell wall thickening is common feature of vancomycin resistance in Staphylococcus aureus. J Clin Microbiol 41:5–14

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Palazzo IC, Araujo ML, Darini AL (2005) First report of vancomycin-resistant staphylococci isolated from healthy carriers in Brazil. J Clin Microbiol 43:179–185

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Nishi H, Komatsuzawa H, Yamada S, Fujiwara T, Ohara M, Ohta K, Sugiyama M, Ishikawa T, Sugai M (2003) Moenomycin-resistance is associated with vancomycin-intermediate susceptibility in Staphylococcus aureus. Microbiol Immunol 47:927–935

    Article  PubMed  CAS  Google Scholar 

  21. Kawai M, Yamada S, Ishidoshiro A, Oyamada Y, Ito H, Yamagishi J (2009) Cell-wall thickness: possible mechanism of acriflavine resistance in methicillin-resistant Staphylococcus aureus. J Med Microbiol 58:331–336

    Article  PubMed  CAS  Google Scholar 

  22. Williams I, Paul F, Lloyd D, Jepras R, Critchley I, Newman M, Warrack J, Giokarini T, Hayes AJ, Randerson PF, Venables WA (1999) Flow cytometry and other techniques show that Staphylococcus aureus undergoes significant physiological changes in the early stages of surface-attached culture. Microbiology 145:1325–1333

    Article  PubMed  CAS  Google Scholar 

  23. Nishino T (1975) An electron microscopic study of antagonism between cephalexin and erythromycin in Staphylococcus aureus. Jpn J Microbiol 19:53–63

    Article  PubMed  CAS  Google Scholar 

  24. Cui L, Murakami H, Kuwahara-Arai K, Hanaki H, Hiramatsu K (2000) Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu50. Antimicrob Agents Chemother 44:2276–2285

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Hanaki H, Kuwahara-Arai K, Boyle-Vavra S, Daum RS, Labischinski H, Hiramatsu K (1998) Activated cell-wall synthesis is associated with vancomycin resistance in methicillin-resistant Staphylococcus aureus clinical strains Mu3 and Mu50. J Antimicrob Chemother 42:199–209

    Article  PubMed  CAS  Google Scholar 

  26. Pfeltz RF, Singh VK, Schmidt JL, Batten MA, Baranyk CS, Nadakavukaren MJ, Jayaswal RK, Wilkinson BJ (2000) Characterization of passage-selected vancomycin-resistant Staphylococcus aureus strains of diverse parental backgrounds. Antimicrob Agents Chemother 44:294–303

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Sieradzki K, Tomasz A (2003) Alterations of cell wall structure and metabolism accompany reduced susceptibility to vancomycin in an isogenic series of clinical isolates of Staphylococcus aureus. J Bacteriol 185:7103–7110

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Hanaki H, Labischinski H, Inaba Y, Kondo N, Murakami H, Hiramatsu K (1998) Increase in glutamine-non-amidated muropeptides in the peptidoglycan of vancomycin-resistant Staphylococcus aureus strain Mu50. J Antimicrob Chemother 42:315–320

    Article  PubMed  CAS  Google Scholar 

  29. Chaieb K, Zmantar T, Chehab O, Bouchami O, Ben Hasen A, Mahdouani K, Bakhrouf A (2007) Antibiotic resistance genes detected by multiplex PCR assay in Staphylococcus epidermidis strains isolated from dialysis fluid and needles in a dialysis service. Jpn J Infect Dis 60:183–187

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Mr. K. Uehira, Mr. T. Suda and Ms. K. Yamane from the Electron Microscope Centre, and Ms. S. Ohmori from the Department of Microbiology, Kawasaki Medical School, for excellent technical assistance. This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports and Technology Japan (21592183, 23791947) and research project grants 19-404M, 20-411I and 23S-2 from Kawasaki Medical School, Japan.

Author information

Authors and Affiliations

  1. Department of Otolaryngology, Kawasaki Medical School, 577 Matsusima, Kurasiki, Okayama, 701-0192, Japan

    Yukiyoshi Hyo, Kenji Fukutsuji & Tamotsu Harada

  2. Department of Microbiology, Kawasaki Medical School, 577 Matsusima, Kurasiki, Okayama, Japan

    Yukiyoshi Hyo & Sakuo Yamada

  3. Department of Clinical Nutrition, Kawasaki University of Medical Welfare, 288 Matsusima, Kurasiki, Okayama, Japan

    Sakuo Yamada

Authors
  1. Yukiyoshi Hyo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sakuo Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenji Fukutsuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tamotsu Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yukiyoshi Hyo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hyo, Y., Yamada, S., Fukutsuji, K. et al. Thickening of the cell wall in macrolide-resistant Staphylococcus aureus . Med Mol Morphol 46, 217–224 (2013). https://doi.org/10.1007/s00795-013-0027-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-013-0027-y

Keywords

Search

Navigation