BMVC與其衍生物增強光動力殺菌之探討

Abstract

目前臨床上面對微生物的感染主要是使用抗生素來進行治療。為了解決近來抗藥性的問題，光動力殺菌逐漸受到重視並成為治療微生物感染另一項選擇。光動力殺菌與傳統抗生素殺菌的作用機制不同，主要是當光感物質受到特定波長光線激發後，可迅速產生單態氧與自由基對微生物造成嚴重破壞，進一步達到毒殺的效果。 BMVC為一對正常細胞毒性很低、且帶正電的小分子化合物。由本研究的結果發現，BMVC確實能夠增強光動力對革蘭氏陽性菌的殺菌效果，其中也包括抗藥性菌株。然而對於革蘭氏陰性菌綠膿桿菌並無明顯殺菌效果。BMVC十二個長碳鏈的衍生物 (BMVC-12C) 經標準藥物敏感性測試，實驗結果發現針對金黃色葡萄球菌之最低殺菌濃度為8 ug/ml，顯示此藥物對於金黃色葡萄球菌具有明顯的毒殺效果。實驗結果也發現BMVC-12C之殺菌效果與菌數有很大關聯。此外，我們也發現BMVC-12C在培養液中之殺菌效果不佳，可能是受到培養液中蛋白質或其他物質的干擾。因此未來在臨床的治療上，應首要解決血液或組織中蛋白質的干擾，以提高此類藥物的殺菌能力與應用價值。

Presently, antibiotics are the most common antimicrobial agents used for the treatment of infection caused by bacteria and fungi. However, the growing of drug-resistance among pathogenic microorganisms has become a significant problem due to the improper use of antibiotics. Photodynamic inactivation (PDI) is an alternative antimicrobial treatment based on the excitation of photosensitizers (PSs) after irradiated with an appropriate wavelength of light. This process can generate reactive oxygen species to destroy and kill microorganisms. 3,6-bis (1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) is a small molecule with positive charge, and with very low toxicity toward normal cells. In this study, we investigate the possibility of using BMVC as an antimicrobial agent. We found that BMVC can enhance the TBO-mediated photodynamic inhibition against gram-positive bacteria and antibiotics resistant strains. In addition, we also found that BMVC derivative, BMVC-12C alone, has bactericidal effect against gram-positive bacteria. The minimum bactericidal concentration of BMVC-12C against Staphylococcus aereus is about 8 ug/ml. However, the antibacterial efficacy of BMVC-12C was reduced in culture medium compared to that of PBS. This may be due to the interference of proteins in medium.