한국미생물·생명공학회지 (Microbiology and Biotechnology Letters)

  • 제41권1호
  • /
  • Pages.88-95
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  • 2013
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  • 1598-642X(pISSN)
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  • 2234-7305(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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세포벽 (1,3)-${\beta}$-D-Glucan Polymer 합성의 저해로 인한 황금(Scutellaria baicalensis)의 항바이오필름 활성

Antibiofilm Activity of Scutellaria baicalensis through the Inhibition of Synthesis of the Cell Wall (1, 3)-${\beta}$-D-Glucan Polymer

  • Kim, Younhee (Department of Oriental Medicine, Semyung University)
  • 투고 : 2012.09.25
  • 심사 : 2012.11.02
  • 발행 : 2013.03.28
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초록

Candida 바이오필름은 숙주조직과 의료기기의 표면에 자라는 자가-조직화된 미생물의 군락으로 전통적인 항진균제에 대한 저항성이 높게 나타난다. 황금(Scutellaria baicalensis)의 뿌리는 극동지방에서 의료용 목적으로 널리 사용되어 왔다. 본 연구의 목적은 10 C. albicans 임상 분리균주에 의해 형성된 바이오필름에 대한 황금의 수용성 추출물의 효과를 평가하고, 항바이오필름 활성에 대한 메커니즘을 알아보는 것이다. 바이오필름에 대한 효과는 XTT 환원분석법을 사용하였으며, 조사된 모든 균주에 대한 대사활성은 MIC에서 유의하게 감소($57.7{\pm}17.3$%)하였다. 황금추출물은 (1,3)-${\beta}$-D-글루칸 합성효소의 활성을 저해하였고 C. albicans의 형태에 대한 황금의 효과는 글루칸 합성의 억제로 인한 생장의 변화와 관련이 있었다: 대부분의 세포는 둥글고 팽창되었으며 세포벽이 진하게 염색되거나 파열되었다. 항캔디다 활성은 살진균성이었고, 황금은 C. albicans를 $G_0/G_1$기에 머물게 했다. 데이터는 황금이 목표가 되는 균류에 다중의 치명적인 효과를 내며, (1,3)-${\beta}$-D-글루칸 합성효소의 활성을 저해함을 통해 궁극적으로는 세포벽의 파열과 죽음에 이르게 한다는 것을 나타낸다. 따라서 황금은 바이오필름과 관련된 캔디다의 감염을 치료하고 제거하기 위한 항진균제 개발 후보 물질로서의 가능성을 가진다.

Candida biofilms are self-organized microbial communities growing on the surfaces of host tissues and medical devices. These biofilms have been displaying increasing resistance against conventional antifungal agents. The roots of Scutellaria baicalensis have been widely used for medicinal purpose throughout East Asia. The aim of the present study was to evaluate the effect of S. baicalensis aqueous extract upon the preformed biofilms of 10 clinical C. albicans isolates, and assess the mechanism of the antibiofilm activity. Its effect on preformed biofilm was judged using an XTT reduction assay and the metabolic activity of all tested strains were reduced ($57.7{\pm}17.3$%) at MIC values. The S. baicalenis extract inhibited (1, 3)-${\beta}$-D-glucan synthase activity. The effect of S. baicalensis on the morphology of C. albicans was related to the changes in growth caused by inhibiting glucan synthesis; most cells were round and swollen, and cell walls were densely stained or ruptured. The anticandidal activity was fungicidal, and the extract also arrested C. albicans cells at $G_0/G_1$. The data suggest that S. baicalensis has multiple fatal effects on target fungi, which ultimately result in cell wall disruption and killing by inhibiting (1, 3)-${\beta}$-D-glucan synthesis. Therefore, S. baicalensis holds great promise for use in treating and eliminating biofilm-associated Candida infections.

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참고문헌

  1. Beaulieu, D., J. Tang, S. B. Yan, J. M. Vessels, J. A. Radding, and T. R. Parr, Jr. 1994. Characterization and cilofungin inhibition of solubilized Aspergillus fumigatus (1,3)-$\beta$-D-glucan synthase. Antimicrob. Agents Chemother. 38: 937-944. https://doi.org/10.1128/AAC.38.5.937
  2. Blankenship, J. R. and A. P. Mitchell. 2006. How to build a biofilm: a fungal perspective. Curr. Opin. Microbiol. 9: 588-594. https://doi.org/10.1016/j.mib.2006.10.003
  3. Calderone, R. A. and P. C. Braun. 1991. Adherence and receptor relationships of Candida albicans. Microbiol. Rev. 55: 1-20.
  4. Calderone, R. A. and W. A. Fonzi. 2001. Virulence factors of Candida albicans. Trends Microbiol. 9: 327-335. https://doi.org/10.1016/S0966-842X(01)02094-7
  5. Chandra, J., D. M. Kuhn, P. K. Mukherjee, L. L. Hoyer, T. McCormick, and M. A. Ghannoum. 2001. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J. Bacteriol. 183: 5385-5394. https://doi.org/10.1128/JB.183.18.5385-5394.2001
  6. CLSI. 2008a. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard-third edition; CLSI document M27-A3. Clinical and Laboratory Standards Institute, Wayne.
  7. Douglas, C. M., F. Foor, J. A. Marrinan, N. Morin, J. B. Nielsen, A. M. Dahl, P. Mazur, W. Baginsky, W. Li, and M. el-Sherbeini. 1994. The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1, 3- $\beta$-D-glucan synthase. Proc. Natl. Acad. Sci. U.S.A. 91: 12907- 12911. https://doi.org/10.1073/pnas.91.26.12907
  8. Douglas, L. J. 2003. Candida biofilms and their role in infection. Trends Microbiol. 11: 30-36. https://doi.org/10.1016/S0966-842X(02)00002-1
  9. Guarrera, P. M. 2005. Traditional phytotherapy in central Italy. Fitotherapia 76: 1-25. https://doi.org/10.1016/j.fitote.2004.09.006
  10. Haynes, K. 2001. Virulence in Candida species. Trends Microbiol. 9: 591-596. https://doi.org/10.1016/S0966-842X(01)02237-5
  11. Henry-Stanley, M. J., R. M. Garni, and C. L. Wells. 2004. Adaptation of FUN-1 and Calcofluor white stains to assess the ability of viable and nonviable yeast to adhere to and be internalized by cultured mammalian cells. J. Microbiol. Methods 59: 289-292. https://doi.org/10.1016/j.mimet.2004.07.001
  12. Huang, W. H., Lee, A. R., and C. H. Yang. 2006. Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI. Biosci. Biotechnol. Biochem. 70: 2371-2380. https://doi.org/10.1271/bbb.50698
  13. Klis, F. M., A. F. J. Ram., and P. W. J. De Groot. 2007. A molecular and genomic view of the fungal cell wall. The Mycota 8: 97-120. https://doi.org/10.1007/978-3-540-70618-2_4
  14. Kolotila, M. P., C. W. Smith, and A. L. Rogers. 1987. Candidacidal activity of macrophages from three mouse strains as demonstrated by a new method: neutral red staining. Med. Mycol. 25: 283-290 https://doi.org/10.1080/02681218780000321
  15. Krcmery, V. and A. J. Barnes. 2002. Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. J. Hosp. Infect. 50: 243-260. https://doi.org/10.1053/jhin.2001.1151
  16. Kurtz, M. B., C. Douglas, J. Marrinan, K. Nollstadt, J. Onishi, S. Dreikorn, J. Milligan, S. Mandala, J. Thompson, and J. M. Balkovec. 1994. Increased antifungal activity of L-733,560, a water-soluble, semisynthetic pneumocandin, is due to enhanced inhibition of cell wall synthesis. Antimicrob. Agents Chemother. 38: 2750-2757. https://doi.org/10.1128/AAC.38.12.2750
  17. Liu, M., V. Seidel, D. R. Katerere, and A. I. Gray. 2007. Colorimetric broth microdilution for the antifungal screening of plant extracts against yeast. Methods 42: 325-329. https://doi.org/10.1016/j.ymeth.2007.02.013
  18. Mahmoud, A. G. and B. R. Louis. 1999. Antifungal agents: mode of action, mechanism of resistance, and correlation of these mechanisms with bacterial resistance. Clin. Microbiol. Rev. 12: 501-517.
  19. Millard, P. J., B. L. Roth, H. -P. Thi, S. T. Yue, and R. P. Haugland. 1997. Development of the FUN-1 family of fluorescent probes for vacuole labeling and viability testing of yeast. Appl. Environ. Microbiol. 63: 2897-2905.
  20. O'Brien, J., J. Wilson, T. Orton, and F. Pognan. 2000. Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur. J. Biochem. 267: 5421-5426. https://doi.org/10.1046/j.1432-1327.2000.01606.x
  21. Oliver, B. G., P. M. Silver, C. Marie, S. J. Hoot, S. E. Leyde, and T. C. White. 2008. Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi. Microbiol. 154: 960-970. https://doi.org/10.1099/mic.0.2007/013805-0
  22. Park, S. J., S. J. Choi, W. S. Shin, H. M. Lee, K. S. Lee, and K. H. Lee. 2009. Relationship between biofilm formation ability and virulence of Candida albicans. J. Bacteriol. Virol. 39: 119-124. https://doi.org/10.4167/jbv.2009.39.2.119
  23. Pfaller, M. A. and D. J. Diekema. 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 20: 133-163. https://doi.org/10.1128/CMR.00029-06
  24. Ramage, G., J. P. Martinez, and J. L. Lopez-Ribot. 2006. Candida biofilms on implanted biomaterials: a clinically significant problem. FEMS Yeast Res. 6: 979-986. https://doi.org/10.1111/j.1567-1364.2006.00117.x
  25. Ramage, G., K. Vande-Walle, B. L. Wickes, and J. L. Lopez-Ribot. 2001. Standardized method for in vitro antifungal susceptibility testing of Candida albicans biofilms. Antimicrob. Agents Chemother. 45: 2475-2479. https://doi.org/10.1128/AAC.45.9.2475-2479.2001
  26. Roling, E. E., M. E. Klepser, A. Wasson, R. E. Lewes, E. J. Ernst, and M. A. Pfaller. 2002. Antifungal activities of fluconazole, caspofungin (MK0991), and anidulafungin (LY303366) alone and in combination against Candida spp. and Cryotococcus neoformans via time-kill methods. Diagn. Microbial. Infec. Dis. 43: 13-17. https://doi.org/10.1016/S0732-8893(02)00361-9
  27. Shedletzky, E., C. Unger, and D. P. Delmer. 1997. A microtiterbased fluorescence assay for (1,3)-$\beta$-glucan synthases. Anal. Biochem. 249: 88-93. https://doi.org/10.1006/abio.1997.2162
  28. Tang, J. and T. R. Parr, Jr. 1991. W-1 solubilization and kinetics of inhibition by cilofungin of Candida albicans (1,3)-$\beta$-D-glucan synthase. Antimicrob. Agents Chemother. 35: 99-103. https://doi.org/10.1128/AAC.35.1.99
  29. Yoon, S. B., Y. J. Lee, S. K. Park, H. C. Kim, H. Bae, H. M. Kim, S. G. Ko, H. Y. Choi, M. S. Oh, and W. Park. 2009. Anti-inflammatory effects of Scutellaria baicalensis water extract on LPSactivated RAW 264.7 macrophages. J. Ethnopharmacol. 125: 286-290. https://doi.org/10.1016/j.jep.2009.06.027

피인용 문헌

  1. Extraction solvent-dependent antioxidant activities and cancer cell growth inhibitory effects of Scutellaria baicalensis extracts vol.26, pp.5, 2019, https://doi.org/10.11002/kjfp.2019.26.5.566