【研究發表】本系博士班洪茂軒同學研究成果發表－台灣海洋弧菌的偽胜肽與市售抗生素的合併治療效果
摘要
在此次研究中，我們從台灣週邊的海洋環境中採集14株海洋弧菌，在初步的生物活性測試顯示，其具有許多生物活性作用，例如鐵螯合和抗菌活性。利用 16S rDNA 定序，建立了這些海洋弧菌的基因樹分析，並與藉由 MALDI-TOF 的分析所繪製出弧菌菌株質譜圖 (MSP)進行比較，發現MSP分類與其生物活性有較強的相關性。透過 LC-HRMS/MS 與 GNPS 分子網絡分析，三株菌株(Vibrio tubiashii DJW05-1、V. japonicas DJW05-8 和 V. fortis DJW21-4) 有著相似的抗菌活性化合物：偽胜肽，利用活性導引與管柱層析，我們分離出新的不飽和的diketopiperazine, (Z)-3-(2-methylpropylidene)-2, 3-dihydropyrrolo[1,2-a] pyrazine-1,4-dione，以及一系列diketopiperazine 和 new annotated pseudopeptide，以及三種pseudopeptide (andrimid、moiramide B、moiramide C)及 alkaloids。在進一步的抗菌試驗與商用抗生素合併測試中，andrimid對S. aureus, E. coli, S. typhimurium, 與 A. baumannii 具有抑制作用，P. aeruginosa無效，儘管如此，andrimid與商用抗生素仍有協同或加成作用，此發現為在醫學應用有很大的發展潛力。
Abstract
Vibrio strains, identified by 16S rDNA, were isolated from the marine environment surrounding Taiwan, revealing diverse bioactive effects, such as iron-chelating and antimicrobial activities. Notably, the hierarchical clustering dendrogram of mass spectrum profiles (MSP) of the Vibrio strains using MALDI-TOF, in contrast to the phylogenetic tree based on 16S rDNA sequencing analysis, exhibited a strong correlation with their observed bioactivities. Within this set, GNPS molecular network analysis by LC-HRMS/MS highlighted that three strains, Vibrio tubiashii DJW05-1, V. japonicas DJW05-8, and V. fortis DJW21-4 shared similar bioactive pseudopeptides in the same cluster. Subsequent chromatographical isolation and purification yield an unprecedented unsaturated diketopiperazine, (Z)-3-(2-methylpropylidene)-2,3-dihydropyrrolo[1,2-a]pyrazine-1,4-dione (1), along with a series of diketopiperazines, and a potential new annotated pseudopeptide 2, as well as three pseudopeptides, including andrimid (10), moiramide B (11), and moiramide C (12), and several alkaloids from V. tubiashii DJW05-1. Further investigation into the combined applications of the major antimicrobial compound and commercial antibiotics revealed that andrimid (10) displayed significant inhibitory effects against Gram-positive Staphylococcus aureus, and Gram-negative Escherichia coli, Salmonella typhimurium, and Acinetobacter baumannii, except for Pseudomonas aeruginosa. Nevertheless, the potential for synergistic and additive effects of andrimid (10) with certain antibiotics remains, presenting valuable prospects for medicinal applications.
