1887

Abstract

Meticillin-resistant (MRSA) biofilm formation in humans is of serious clinical concern. Previous studies have been performed with biofilms grown only on inorganic substrates; therefore, we investigated the vancomycin (VCM) resistance of MRSA biofilms grown on skin tissue.

We established a novel tissue substrate model, namely MRSA grown on segments of mouse skin tissue (dermal chips, DCs), and compared its resistance capacity against VCM with that of MRSA biofilms grown on plastic chips (PCs).

For one MRSA isolate, we found that the VCM MIC was identical (1.56 µg ml) for planktonic cultures and for biofilms-formed on PCs (PC-BF), although the minimum bactericidal concentration (MBC) increased to 6.25 µg ml in PC-BF. On the contrary, the MIC and MBC for biofilms formed on DCs (DC-BF) significantly increased (25 and 50 µg ml, respectively). Furthermore, the minimum biofilm-eradicating concentration was higher for DC-BF (100 µg ml) than for PC-BF (25 µg ml). Using six MRSA strains, we found that in PC-BF, the c.f.u. number decreased with increasing VCM concentration, whereas in DC-BF, it greatly increased until the MIC was reached, accompanied by the formation of large colonies, thicker bacterial walls and the presence of many mitotic cells.

Our results indicate that the VCM resistance of MRSA was greater in DC-BF. We conclude that DCs may provide a specific environment for MRSA that enhances bacterial growth under cytotoxic VCM concentrations, and might be useful for the study of skin wound infections and the effects of antimicrobial drugs.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000461
2017-04-01
2024-05-03
Loading full text...

Full text loading...

/deliver/fulltext/jmm/66/4/542.html?itemId=/content/journal/jmm/10.1099/jmm.0.000461&mimeType=html&fmt=ahah

References

  1. Utsui Y, Yokota T. Role of an altered penicillin-binding protein in methicillin- and cephem-resistant Staphylococcus aureus. Antimicrob Agents Chemother 1985; 28:397–403 [View Article][PubMed]
    [Google Scholar]
  2. Moellering RC. Vancomycin: a 50-year reassessment. Clin Infect Dis 2006; 42:S3–S4 [View Article][PubMed]
    [Google Scholar]
  3. Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF et al. 2015 infectious diseases society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis 2015; 61:e26e46 [View Article][PubMed]
    [Google Scholar]
  4. Gould IM. Clinical activity of anti-gram-positive agents against methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 2011; 66:iv17–iv21 [View Article][PubMed]
    [Google Scholar]
  5. Stevens DL. The role of vancomycin in the treatment paradigm. Clin Infect Dis 2006; 42:S51–S57 [View Article][PubMed]
    [Google Scholar]
  6. Limoli DH, Jones CJ, Wozniak DJ. Bacterial extracellular polysaccharides in biofilm formation and function. Microbiol Spectr 2015; 3:MB-0011-2014
    [Google Scholar]
  7. Stewart PS. Mechanisms of antibiotic resistance in bacterial biofilms. Int J Med Microbiol 2002; 292:107–113 [View Article][PubMed]
    [Google Scholar]
  8. Singh R, Ray P, Das A, Sharma M. Role of persisters and small-colony variants in antibiotic resistance of planktonic and biofilm-associated Staphylococcus aureus: an in vitro study. J Med Microbiol 2009; 58:1067–1073 [View Article][PubMed]
    [Google Scholar]
  9. Garcia LG, Lemaire S, Kahl BC, Becker K, Proctor RA et al. Antibiotic activity against small-colony variants of Staphylococcus aureus: review of in vitro, animal and clinical data. J Antimicrob Chemother 2013; 68:1455–1464 [View Article][PubMed]
    [Google Scholar]
  10. Cucarella C, Solano C, Valle J, Amorena B, Lasa I et al. Bap, a Staphylococcus aureus surface protein involved in biofilm formation. J Bacteriol 2001; 183:2888–2896 [View Article][PubMed]
    [Google Scholar]
  11. Foster TJ, Geoghegan JA, Ganesh VK, Höök M. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat Rev Microbiol 2014; 12:49–62 [View Article][PubMed]
    [Google Scholar]
  12. Foster TJ, Höök M. Surface protein adhesins of Staphylococcus aureus. Trends Microbiol 1998; 6:484–488 [View Article][PubMed]
    [Google Scholar]
  13. Makino T, Jimi S, Oyama T, Nakano Y, Hamamoto K et al. Infection mechanism of biofilm-forming Staphylococcus aureus on indwelling foreign materials in mice. Int Wound J 2015; 12:122–131 [View Article][PubMed]
    [Google Scholar]
  14. Oyama T, Miyazaki M, Yoshimura M, Takata T, Ohjimi H et al. Biofilm-forming methicillin-resistant Staphylococcus aureus survive in Kupffer cells and exhibit high virulence in mice. Toxins 2016; 8:198 [View Article][PubMed]
    [Google Scholar]
  15. Stewart PS, Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet 2001; 358:135–138 [View Article][PubMed]
    [Google Scholar]
  16. Hall-Stoodley L, Stoodley P. Evolving concepts in biofilm infections. Cell Microbiol 2009; 11:1034–1043 [View Article][PubMed]
    [Google Scholar]
  17. Jones SM, Morgan M, Humphrey TJ, Lappin-Scott H. Effect of vancomycin and rifampicin on meticillin-resistant Staphylococcus aureus biofilms. Lancet 2001; 357:40–41 [View Article][PubMed]
    [Google Scholar]
  18. Howden BP, Johnson PD, Ward PB, Stinear TP, Davies JK. Isolates with low-level vancomycin resistance associated with persistent methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 2006; 50:3039–3047 [View Article][PubMed]
    [Google Scholar]
  19. Mishra NN, Yang SJ, Sawa A, Rubio A, Nast CC et al. Analysis of cell membrane characteristics of in vitro-selected daptomycin-resistant strains of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2009; 53:2312–2318 [View Article][PubMed]
    [Google Scholar]
  20. Onyango LA, Hugh Dunstan R, Roberts TK, Macdonald MM, Gottfries J. Phenotypic variants of staphylococci and their underlying population distributions following exposure to stress. PLoS One 2013; 8:e77614 [View Article][PubMed]
    [Google Scholar]
  21. Wang Q, Sun FJ, Liu Y, Xiong LR, Xie LL et al. Enhancement of biofilm formation by subinhibitory concentrations of macrolides in icaADBC-positive and -negative clinical isolates of Staphylococcus epidermidis. Antimicrob Agents Chemother 2010; 54:2707–2711 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000461
Loading
/content/journal/jmm/10.1099/jmm.0.000461
Loading

Data & Media loading...

Supplements

Supplementary File 1

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