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Volume 161, Issue 2

Inhibition of polysaccharide synthesis by the orthologue PGN_0088 is indirectly associated with the penetration of biofilms by macrolide antibiotics Free

Abstract

Microbes commonly adhere to surfaces, aggregate in self-produced extracellular polymeric substances (EPS) and live in biofilms. Periodontitis is a serious oral infection that is initiated by the formation of biofilms by . EPS act as a barrier that protects biofilm-forming cells against sources of stress, including those induced by host immune cells and antimicrobial agents. Therefore, drugs intended to kill such micro-organisms cannot be used for the treatment of biofilm infections. Our previous studies revealed that subminimal inhibitory concentrations (subMIC) of two macrolide antibiotics (azithromycin, AZM and erythromycin, ERY) reduced biofilms. Furthermore, we demonstrated that the orthologue (PGN_0088) inhibits the synthesis of carbohydrates that are components of EPS in biofilms. Here, we constructed a novel mutant from ATCC 33277 and reveal that the increased abundance of carbohydrate in EPS of the mutant led to a reduced infiltration rate of AZM and ERY through EPS, and consequently elevated biofilm resistance to these macrolides. Detailed elucidation of the interaction between the product of the gene and EPS will assist in the development of novel approaches that target EPS to prevent and inhibit the formation of biofilms.

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© 2015 The Authors
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2015-02-01
2024-05-08
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References

  1. Anderl J. N., Franklin M. J., Stewart P. S. 2000; Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrob Agents Chemother 44:1818–1824 [View Article][PubMed]
     [Google Scholar]
  2. Brown M. R., Allison D. G., Gilbert P. 1988; Resistance of bacterial biofilms to antibiotics: a growth-rate related effect?. J Antimicrob Chemother 22:777–780 [View Article][PubMed]
     [Google Scholar]
  3. Characklis W. G. 1990; Microbial biofouling control. In Biofilms pp. 585–633 Edited by Characklis W. G., Marshall K. C. New York: Wiley;
     [Google Scholar]
  4. Close T. J., Rodriguez R. L. 1982; Construction and characterization of the chloramphenicol-resistance gene cartridge: A new approach to the transcriptional mapping of extrachromosomal elements. Gene 20:305–316 [CrossRef]
     [Google Scholar]
  5. Chu F., Kearns D. B., Branda S. S., Kolter R., Losick R. 2006; Targets of the master regulator of biofilm formation in Bacillus subtilis. . Mol Microbiol 59:1216–1228 [View Article][PubMed]
     [Google Scholar]
  6. Chu F., Kearns D. B., McLoon A., Chai Y., Kolter R., Losick R. 2008; A novel regulatory protein governing biofilm formation in Bacillus subtilis. . Mol Microbiol 68:1117–1127 [View Article][PubMed]
     [Google Scholar]
  7. Costerton J. W., Irvin R. T., Cheng K. J. 1981; The bacterial glycocalyx in nature and disease. Annu Rev Microbiol 35:299–324 [View Article][PubMed]
     [Google Scholar]
  8. Costerton J. W., Cheng K. J., Geesey G. G., Ladd T. I., Nickel J. C., Dasgupta M., Marrie T. J. 1987; Bacterial biofilms in nature and disease. Annu Rev Microbiol 41:435–464 [View Article][PubMed]
     [Google Scholar]
  9. Costerton J. W., Lewandowski Z., Caldwell D. E., Korber D. R., Lappin-Scott H. M. 1995; Microbial biofilms. Annu Rev Microbiol 49:711–745 [View Article][PubMed]
     [Google Scholar]
  10. Costerton J. W., Stewart P. S., Greenberg E. P. 1999; Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322 [View Article][PubMed]
     [Google Scholar]
  11. Donlan R. M., Costerton J. W. 2002; Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 15:167–193 [View Article][PubMed]
     [Google Scholar]
  12. Flemming H. C., Wingender J. 2010; The biofilm matrix. Nat Rev Microbiol 8:623–633[PubMed]
     [Google Scholar]
  13. Ichimiya T., Takeoka K., Hiramatsu K., Hirai K., Yamasaki T., Nasu M. 1996; The influence of azithromycin on the biofilm formation of Pseudomonas aeruginosa in vitro. Chemotherapy 42:186–191 [View Article][PubMed]
     [Google Scholar]
  14. Li Y. H., Tang N., Aspiras M. B., Lau P. C., Lee J. H., Ellen R. P., Cvitkovitch D. G. 2002; A quorum-sensing signaling system essential for genetic competence in Streptococcus mutans is involved in biofilm formation. J Bacteriol 184:2699–2708 [View Article][PubMed]
     [Google Scholar]
  15. Lopez D., Vlamakis H., Kolter R. 2009; Generation of multiple cell types in Bacillus subtilis. . FEMS Microbiol Rev 33:152–163 [View Article][PubMed]
     [Google Scholar]
  16. Lynch S. V., Dixon L., Benoit M. R., Brodie E. L., Keyhan M., Hu P., Ackerley D. F., Andersen G. L., Matin A. 2007; Role of the rapA gene in controlling antibiotic resistance of Escherichia coli biofilms. Antimicrob Agents Chemother 51:3650–3658 [View Article][PubMed]
     [Google Scholar]
  17. Maezono H., Noiri Y., Asahi Y., Yamaguchi M., Yamamoto R., Izutani N., Azakami H., Ebisu S. 2011; Antibiofilm effects of azithromycin and erythromycin on Porphyromonas gingivalis. . Antimicrob Agents Chemother 55:5887–5892 [View Article][PubMed]
     [Google Scholar]
  18. Mah T. F., O’Toole G. A. 2001; Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 9:34–39 [View Article][PubMed]
     [Google Scholar]
  19. Nagano K., Murakami Y., Nishikawa K., Sakakibara J., Shimozato K., Yoshimura F. 2007; Characterization of RagA and RagB in Porphyromonas gingivalis: study using gene-deletion mutants. J Med Microbiol 56:1536–1548 [View Article][PubMed]
     [Google Scholar]
  20. Noguchi N., Noiri Y., Narimatsu M., Ebisu S. 2005; Identification and localization of extraradicular biofilm-forming bacteria associated with refractory endodontic pathogens. Appl Environ Microbiol 71:8738–8743 [View Article][PubMed]
     [Google Scholar]
  21. Noiri Y., Ozaki K., Nakae H., Matsuo T., Ebisu S. 1997; An immunohistochemical study on the localization of Porphyromonas gingivalis, Campylobacter rectus and Actinomyces viscosus in human periodontal pockets. J Periodontal Res 32:598–607 [View Article][PubMed]
     [Google Scholar]
  22. Noiri Y., Ehara A., Kawahara T., Takemura N., Ebisu S. 2002; Participation of bacterial biofilms in refractory and chronic periapical periodontitis. J Endod 28:679–683 [View Article][PubMed]
     [Google Scholar]
  23. Noiri Y., Okami Y., Narimatsu M., Takahashi Y., Kawahara T., Ebisu S. 2003; Effects of chlorhexidine, minocycline, and metronidazole on Porphyromonas gingivalis strain 381 in biofilms. J Periodontol 74:1647–1651 [View Article][PubMed]
     [Google Scholar]
  24. Noiri Y., Li L., Yoshimura F., Ebisu S. 2004; Localization of Porphyromonas gingivalis-carrying fimbriae in situ in human periodontal pockets. J Dent Res 83:941–945 [View Article][PubMed]
     [Google Scholar]
  25. O’Toole G., Kaplan H. B., Kolter R. 2000; Biofilm formation as microbial development. Annu Rev Microbiol 54:49–79 [View Article][PubMed]
     [Google Scholar]
  26. Samaranayake Y. H., Ye J., Yau J. Y., Cheung B. P., Samaranayake L. P. 2005; In vitro method to study antifungal perfusion in Candida biofilms. J Clin Microbiol 43:818–825 [View Article][PubMed]
     [Google Scholar]
  27. Simon R., Priefer U., Pühler A. 1983; A broad host range mobilization system for in vivo genetic engineering: transposon mutagenesis in gram negative bacteria. Nat Biotechnol 1:784–791 [View Article]
     [Google Scholar]
  28. Starner T. D., Shrout J. D., Parsek M. R., Appelbaum P. C., Kim G. 2008; Subinhibitory concentrations of azithromycin decrease nontypeable Haemophilus influenzae biofilm formation and Diminish established biofilms. Antimicrob Agents Chemother 52:137–145 [View Article][PubMed]
     [Google Scholar]
  29. Stewart P. S., Costerton J. W. 2001; Antibiotic resistance of bacteria in biofilms. Lancet 358:135–138 [View Article][PubMed]
     [Google Scholar]
  30. Winkelman J. T., Blair K. M., Kearns D. B. 2009; RemA (YlzA) and RemB (YaaB) regulate extracellular matrix operon expression and biofilm formation in Bacillus subtilis. . J Bacteriol 191:3981–3991 [View Article][PubMed]
     [Google Scholar]
  31. Yamaguchi M., Sato K., Yukitake H., Noiri Y., Ebisu S., Nakayama K. 2010; A Porphyromonas gingivalis mutant defective in a putative glycosyltransferase exhibits defective biosynthesis of the polysaccharide portions of lipopolysaccharide, decreased gingipain activities, strong autoaggregation, and increased biofilm formation. Infect Immun 78:3801–3812 [View Article][PubMed]
     [Google Scholar]
  32. Yamaguchi M., Noiri Y., Kuboniwa M., Yamamoto R., Asahi Y., Maezono H., Hayashi M., Ebisu S. 2013; Porphyromonas gingivalis biofilms persist after chlorhexidine treatment. Eur J Oral Sci 121:162–168 [View Article][PubMed]
     [Google Scholar]
  33. Yamamoto R., Noiri Y., Yamaguchi M., Asahi Y., Maezono H., Ebisu S. 2011; Time course of gene expression during Porphyromonas gingivalis strain ATCC 33277 biofilm formation. Appl Environ Microbiol 77:6733–6736 [View Article][PubMed]
     [Google Scholar]
  34. Yamamoto R., Noiri Y., Yamaguchi M., Asahi Y., Maezono H., Kuboniwa M., Hayashi M., Ebisu S. 2013; The sinR ortholog PGN_0088 encodes a transcriptional regulator that inhibits polysaccharide synthesis in Porphyromonas gingivalis ATCC 33277 biofilms. PLoS ONE 8:e56017 [View Article][PubMed]
     [Google Scholar]
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Inhibition of polysaccharide synthesis by the sinR orthologue PGN_0088 is indirectly associated with the penetration of Porphyromonas gingivalis biofilms by macrolide antibiotics
Microbiology 161, 422 (2015); https://doi.org/10.1099/mic.0.000013
/content/journal/micro/10.1099/mic.0.000013
/content/journal/micro/10.1099/mic.0.000013
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