Hong Xiao, Pei Lv, Xiaobo Liu, Jingyu Yang, Bin Gong, Tiantao Xiong, Jie Wang, Kun Wang, Wanshan Li, Yuyue Qin, Guangying Chen
Vibriosis poses a significant bacterial threat to aquaculture, affecting a diverse range of fish and shellfish. In this study, a novel dibenzo[b,f]oxepin analogue, phylloplaoxepin A (1), and four new 1,4-naphthoquinone analogues, phylloplaquinones A-D (2-5), along with two known compounds 6 and 7 were isolated from the mangrove-derived fungus Quambalaria cyanescens HLLP-241. Compounds 4 and 6 exhibited potent inhibition against V. alginolyticus, with both exhibiting a MIC values of 3.125 (chloramphenicol, MIC = 1.56 μg/mL). Compounds 3 and 5-7 exhibited significant inhibitory effects against V. parahaemolyticus, each with a MIC values of 0.78 μg/mL, comparable to the positive control (chloramphenicol, MIC = 0.78 μg/mL). Mechanistic studies reveal that compound 4 inhibits biofilm formation of V. alginolyticus in a dose-dependent manner, while simultaneously disrupting membrane integrity, depleting ATP, and inducing accumulation of reactive oxygen species (ROS). Transcriptomic analysis, qRT-PCR validation, molecular docking, molecular dynamics simulations, and enzymatic assays collectively demonstrate that SerA is the key functional target of compound 4 in inhibiting the growth of V. alginolyticus.