Antimycobacterial and cytotoxicity activity of microcystins

Background The present work aimed to evaluate the antimycobacterial activity and cytotoxicity of Microcystis aeruginosa toxins, the MC-LR variant and purified extract of [D-Leu1] microcystin-LR. Methods The antimicrobial activity of M. aeruginosa extract and microcystin was evaluated by resazurin microtiter assay against Mycobacterium tuberculosis, M. terrae, M. chelonae and M. kansasii. The cytotoxicity assay was performed by trypan blue exclusion against the HTC cell line. Results Antimicrobial activity was observed in the hexanic extract of M. aeruginosa (RST 9501 strain) against M. tuberculosis, including sensitive and resistant strains with minimal inhibitory concentrations (MIC) between 1.93 μM and 0.06 μM. The high activity of M. aeruginosa hexanic extract could be attributed to the major presence of the toxins MC-LR and [D-Leu1] MC-LR that showed activity at MIC between 53 and 0.42 μM against tested mycobacterial strains. Even at the highest concentration tested, no toxicity of M. aeruginosa extracts was identified against HTC cells. Conclusions These preliminary results suggest that [D-Leu1] MC-LR is a promising candidate for the development of a new antimycobacterial agent.

背景 本项研究旨在评估铜绿微囊藻毒素、MC-LR变异体及[D-Leu1]微囊藻毒素-LR纯化提取物对分枝杆菌的抗微生物活性及细胞毒性。方法 通过甲臘蓝微量板法评估了铜绿微囊藻提取物及微囊藻毒素对结核分枝杆菌、地分枝杆菌、龟分枝杆菌和堪萨斯分枝杆菌的抗菌活性。细胞毒性试验采用锥虫蓝排除法对HTC细胞系进行。结果 铜绿微囊藻（RST 9501菌株）的己烷提取物对结核分枝杆菌显示出抗菌活性，包括敏感和耐药菌株，其最小抑菌浓度（MIC）介于1.93 μM至0.06 μM之间。铜绿微囊藻己烷提取物的活性较高，这主要归因于其中主要存在的毒素MC-LR和[D-Leu1]MC-LR，它们对测试的分枝杆菌菌株在53至0.42 μM的MIC范围内显示出活性。即使在最高浓度的测试中，也未在HTC细胞上检测到铜绿微囊藻提取物的毒性。结论 这些初步结果表明[D-Leu1]MC-LR是开发新型抗分枝杆菌药物的有望候选者。