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钩端螺旋体属DNA修复基因的基因组调查与表达分析

Genomic survey and expression analysis of DNA repair genes in the genus Leptospira.

作者信息

Martins-Pinheiro Marinalva, Schons-Fonseca Luciane, da Silva Josefa B, Domingos Renan H, Momo Leonardo Hiroyuki Santos, Simões Ana Carolina Quirino, Ho Paulo Lee, da Costa Renata M A

机构信息

Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 05508-900, Brazil.

Departamento de Engenharia Química, Escola Politécnica, Universidade de São Paulo, São Paulo, São Paulo, Brazil.

出版信息

Mol Genet Genomics. 2016 Apr;291(2):703-22. doi: 10.1007/s00438-015-1135-2. Epub 2015 Nov 2.

Abstract

Leptospirosis is an emerging zoonosis with important economic and public health consequences and is caused by pathogenic leptospires. The genus Leptospira belongs to the order Spirochaetales and comprises saprophytic (L. biflexa), pathogenic (L. interrogans) and host-dependent (L. borgpetersenii) members. Here, we present an in silico search for DNA repair pathways in Leptospira spp. The relevance of such DNA repair pathways was assessed through the identification of mRNA levels of some genes during infection in animal model and after exposition to spleen cells. The search was performed by comparison of available Leptospira spp. genomes in public databases with known DNA repair-related genes. Leptospires exhibit some distinct and unexpected characteristics, for instance the existence of a redundant mechanism for repairing a chemically diverse spectrum of alkylated nucleobases, a new mutS-like gene and a new shorter version of uvrD. Leptospira spp. shares some characteristics from Gram-positive, as the presence of PcrA, two RecQ paralogs and two SSB proteins; the latter is considered a feature shared by naturally competent bacteria. We did not find a significant reduction in the number of DNA repair-related genes in both pathogenic and host-dependent species. Pathogenic leptospires were enriched for genes dedicated to base excision repair and non-homologous end joining. Their evolutionary history reveals a remarkable importance of lateral gene transfer events for the evolution of the genus. Up-regulation of specific DNA repair genes, including components of SOS regulon, during infection in animal model validates the critical role of DNA repair mechanisms for the complex interplay between host/pathogen.

摘要

钩端螺旋体病是一种新出现的人畜共患病,具有重要的经济和公共卫生影响,由致病性钩端螺旋体引起。钩端螺旋体属属于螺旋体目,包括腐生菌(双曲钩端螺旋体)、致病菌(问号钩端螺旋体)和宿主依赖菌(博氏钩端螺旋体)。在此,我们对钩端螺旋体属的DNA修复途径进行了计算机模拟搜索。通过鉴定动物模型感染期间和暴露于脾细胞后某些基因的mRNA水平,评估了此类DNA修复途径的相关性。搜索是通过将公共数据库中现有的钩端螺旋体属基因组与已知的DNA修复相关基因进行比较来进行的。钩端螺旋体表现出一些独特且意想不到的特征,例如存在一种冗余机制来修复化学性质多样的烷基化核碱基、一个新的mutS样基因和一个新的较短版本的uvrD。钩端螺旋体属具有一些革兰氏阳性菌的特征,如存在PcrA、两个RecQ旁系同源物和两个单链结合蛋白;后者被认为是自然感受态细菌共有的特征。我们发现致病性和宿主依赖菌中与DNA修复相关的基因数量均未显著减少。致病性钩端螺旋体富含参与碱基切除修复和非同源末端连接的基因。它们的进化史表明横向基因转移事件对该属的进化具有显著重要性。在动物模型感染期间,包括SOS调节子成分在内的特定DNA修复基因的上调,证实了DNA修复机制在宿主/病原体复杂相互作用中的关键作用。

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