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日本微生物保藏中心菌株中大肠杆菌素产生基因簇的基因分型及体外遗传毒性分析

Genotyping of a gene cluster for production of colibactin and in vitro genotoxicity analysis of strains obtained from the Japan Collection of Microorganisms.

作者信息

Kawanishi Masanobu, Shimohara Chiaki, Oda Yoshimitsu, Hisatomi Yuuta, Tsunematsu Yuta, Sato Michio, Hirayama Yuichiro, Miyoshi Noriyuki, Iwashita Yuji, Yoshikawa Yuko, Sugimura Haruhiko, Mutoh Michihiro, Ishikawa Hideki, Wakabayashi Keiji, Yagi Takashi, Watanabe Kenji

机构信息

1Graduate School of Science and Radiation Research Center, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai-shi, Osaka, 599-8570 Japan.

2Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

出版信息

Genes Environ. 2020 Mar 11;42:12. doi: 10.1186/s41021-020-00149-z. eCollection 2020.

Abstract

INTRODUCTION

Colibactin is a small genotoxic molecule produced by enteric bacteria, including certain () strains harbored in the human large intestine. This polyketide-peptide genotoxin is considered to contribute to the development of colorectal cancer. The colibactin-producing ( ) microorganisms possess a 54-kilobase genomic island ( gene cluster). In the present study, to assess the distribution of the gene cluster, genotyping analysis was carried out among strains randomly chosen from the Japan Collection of Microorganisms, RIKEN BRC, Japan.

FINDINGS

The analysis revealed that two of six strains possessed a gene cluster. These strains JCM5263 and JCM5491 induced genotoxicity in in vitro micronucleus (MN) tests using rodent CHO AA8 cells. Since the induction level of MN by JCM5263 was high, a bacterial test was carried out with a cell extract of the strain, revealing that the extract had SOS-inducing potency in the tester bacterium.

CONCLUSION

These results support the observations that the gene cluster is widely distributed in nature and having genotoxic potencies is not rare among microorganisms.

摘要

引言

大肠杆菌素是一种由肠道细菌产生的具有基因毒性的小分子,包括人类大肠中携带的某些()菌株。这种聚酮肽基因毒素被认为与结直肠癌的发生发展有关。产生大肠杆菌素的()微生物拥有一个54千碱基的基因组岛(基因簇)。在本研究中,为了评估该基因簇的分布情况,对从日本理化学研究所生物资源中心日本微生物保藏中心随机选取的菌株进行了基因分型分析。

研究结果

分析显示,六株菌株中有两株拥有该基因簇。这两株菌株JCM5263和JCM5491在使用啮齿动物中国仓鼠卵巢AA8细胞进行的体外微核(MN)试验中诱导了基因毒性。由于JCM5263诱导微核的水平较高,因此用该菌株的细胞提取物进行了细菌试验,结果表明该提取物在试验细菌中具有诱导SOS的能力。

结论

这些结果支持了以下观点,即该基因簇在自然界中广泛分布,并且具有基因毒性的能力在微生物中并不罕见。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d23c/7065307/6f5f8db2276b/41021_2020_149_Fig1_HTML.jpg

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