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多粘芽孢杆菌产生的环状脂肽类杀镰孢菌素对哺乳动物细胞的毒性作用模式。

The toxic mode of action of cyclic lipodepsipeptide fusaricidins, produced by Paenibacillus polymyxa, toward mammalian cells.

作者信息

Mikkola R, Andersson M A, Grigoriev P, Heinonen M, Salkinoja-Salonen M S

机构信息

Department of Civil Engineering, School of Engineering, Aalto University, Aalto, Finland.

Department of Food and Environmental Science, University of Helsinki, Helsinki, Finland.

出版信息

J Appl Microbiol. 2017 Aug;123(2):436-449. doi: 10.1111/jam.13498.

DOI:10.1111/jam.13498
PMID:28557348
Abstract

AIMS

Toxigenic strains of Paenibacillus polymyxa were isolated from buildings connected with the symptoms of ill health. Our aim was to identify the toxic compounds of Paenibacillus polymyxa and to describe their toxic actions.

METHODS AND RESULTS

The toxins of Paenibacillus polymyxa were purified and analysed by HPLC and mass spectrometry. Toxic fusaricidins A and B, and LI-F05a with mass ions at m/z 883·7, 897·6 and 897·6, respectively, were found. The cytotoxicity of purified fusaricidins A and B was measured using boar sperm, porcine tubular kidney epithelial cells and murine fibroblasts. The ion channel forming properties of fusaricidins were studied using the black lipid membrane (BLM) technique. Fusaricidins A and B depolarized the mitochondria of boar sperm, porcine tubular kidney epithelial cells and murine fibroblasts at concentrations of 0·5-1 μg ml and caused nuclear fragmentation and induced apoptosis at concentrations of 2·5-5 μg ml . Furthermore, fusaricidins A and B induced K permeating single channels.

CONCLUSIONS

It was concluded that fusaricidins were toxic to mitochondria and induced apoptosis in mammalian cells. It was proposed that the observed toxicity of fusaricidins is due their ion channel forming properties.

SIGNIFICANCE AND IMPACT OF THE STUDY

This paper revealed, for the first time, the mode of action of Paenibacillus polymyxa fusaricidins toxins towards mammalian cells. Fusaricidins, due to their potassium ionophoricity and mitochondria depolarizing impacts, may have contributed to the health damage observed at sites where the producer strains were isolated at high density.

摘要

目的

从与健康问题相关的建筑物中分离出多粘芽孢杆菌的产毒菌株。我们的目的是鉴定多粘芽孢杆菌的有毒化合物并描述其毒性作用。

方法与结果

多粘芽孢杆菌毒素经纯化后,通过高效液相色谱法和质谱法进行分析。发现了有毒的镰刀菌素A和B,以及质荷比分别为m/z 883·7、897·6和897·6的LI-F05a。使用公猪精子、猪肾小管上皮细胞和小鼠成纤维细胞测定了纯化的镰刀菌素A和B的细胞毒性。利用黑脂质膜(BLM)技术研究了镰刀菌素的离子通道形成特性。镰刀菌素A和B在浓度为0·5 - 1μg/ml时使公猪精子、猪肾小管上皮细胞和小鼠成纤维细胞的线粒体去极化,并在浓度为2·5 - 5μg/ml时导致核碎裂并诱导凋亡。此外,镰刀菌素A和B诱导钾离子通透单通道。

结论

得出结论,镰刀菌素对线粒体有毒性并诱导哺乳动物细胞凋亡。有人提出,观察到的镰刀菌素毒性归因于它们的离子通道形成特性。

研究的意义和影响

本文首次揭示了多粘芽孢杆菌镰刀菌素毒素对哺乳动物细胞的作用模式。镰刀菌素由于其钾离子载体特性和线粒体去极化作用,可能导致在分离出高产毒菌株的场所观察到的健康损害。

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