抗生素多黏菌素B具新穎抗鐮孢菌活性

Abstract

鐮孢菌屬(Fusarium)包含F. oxysporum、F. solani、F. graminearum與F. verticillioides等，且會在植物及人體造成嚴重的感染。臨床上，鐮孢菌感染發生的頻率在所有侵入性絲狀真菌的感染中排名第三，僅次於麴菌屬(Aspergillus)及毛黴目(Mucorales)，而感染的病例中以F. solani及F. oxysporum最多；然而，在植物及人類上，對於鐮孢菌感染的治療仍缺乏有效利器。陽離子態的抗菌胜肽多黏菌素B (polymyxin B) 具有抑制白色念珠菌與新型隱球菌的能力，但針對鐮孢菌的效果仍未知。本研究測試多黏菌素B對12株感染人類及植物(香蕉、番茄、瓜類、豆類、小麥及玉米)之鐮孢菌的抗菌能力。透過稀釋平板法、亞甲藍液染色及XTT還原法測試，此藥劑對所有受測菌株皆具殺真菌能力，其中對大部分菌株的最低殺菌濃度為32或64 μg/mL。多黏菌素B可降低鐮孢菌分生孢子的發芽率，且能造成膜系的缺陷，但厚膜孢子不受藥劑影響。多黏菌素B可與posaconazole產生協同作用(synergistic effect)，且具促進藥物fluconazole、voriconazole或amphotericin B對鐮孢菌抑制作用的潛力；多黏菌素B雖在抑制白色念珠菌及隱球菌的效果中與fluconazole有協同作用，然而在鐮孢菌屬中並未發現一樣的情形，顯示酵母菌及絲狀真菌如鐮孢菌在演化中的多樣性。

The genus Fusarium comprises many species, including F. oxysporum, F. solani, F. graminearum, and F. verticillioides, and causes severe infections in plants and humans. In clinical settings, Fusarium is the third most frequent mold to cause invasive fungal infections, after Aspergillus and the Mucorales. F. solani and F. oxysporum are the most prevalent Fusarium species to cause clinical disease. However, few effective antifungal drugs are available to treat both human and plant Fusarium infections. The cationic peptide antibiotic polymyxin B (PMB) exhibits antifungal activity against the human fungal pathogens Candida albicans and Cryptococcus neoformans, but its efficacy against Fusarium species is unknown. In this study, we tested the antifungal activity of PMB against 12 Fusarium strains that infect humans and plants (banana, tomato, melon, pea, wheat, and maize). PMB was fungicidal against all 12 Fusarium strains, with minimum fungicidal concentrations of 32 or 64 μg/mL for most strains tested, as evidenced by broth dilution, methylene blue staining, and XTT reduction assays. PMB can reduce the germination rates of conidia, but not chlamydospores, and can cause defects in cell membrane integrity in Fusarium strains. PMB exhibits synergistic activity with posaconazole, and can potentiate the effect of fluconazole, voriconazole, or amphotericin B against Fusarium species. However, PMB does not show synergistic effects with fluconazole against Fusarium species as it does against Candida glabrata and C. neoformans, indicating evolutionary divergence of mechanisms between yeast pathogens and the filamentous fungus Fusarium.