Rahbar Mohammad Reza, Zarei Mahboubeh, Jahangiri Abolfazl, Khalili Saeed, Nezafat Navid, Negahdaripour Manica, Fattahian Yaser, Savardashtaki Amir, Ghasemi Younes
Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Front Microbiol. 2020 Nov 12;11:560667. doi: 10.3389/fmicb.2020.560667. eCollection 2020.
species are Gram-negative, facultative intracellular pathogens. They are the main cause of brucellosis, which has led to a global health burden. Adherence of the pathogen to the host cells is the first step in the infection process. The bacteria can adhere to various biotic and abiotic surfaces using their outer membrane proteins. Trimeric autotransporter adhesins (TAAs) are modular homotrimers of various length and domain complexity. They are a diverse, and widespread gene family constituting the type Vc secretion pathway. These adhesins have been established as virulence factors in . To date, no comprehensive and exhaustive study has been performed on the trimeric autotransporter family in the genus. In the present study, various bioinformatics tools were used to provide a novel evolutionary insight into the sequence and structure of this protein family in . To this end, a dataset of all trimeric autotransporters from the genomes was built. Analyses included but were not limited to sequence alignment, phylogenetic tree constructions, codon-based test for selection, clustering of the sequences, and structure (primary to quaternary) predictions. Batch analyzes of the dataset suggested the existence of a few structural domains within the whole population. BatA from the 2308 genome was selected as a reference to describe the features of these structural domains. Furthermore, we examined the structural basis for the observed rigidity and resiliency of the protein structure through a molecular dynamics evaluation, which led us to deduce that the random drift results in the non-adaptive evolution of the trimeric autotransporter genes in the genus. Notably, the modifications have occurred across the genus without interference of gene transmission.
该属细菌为革兰氏阴性兼性胞内病原体。它们是布鲁氏菌病的主要病因,给全球健康带来了负担。病原体黏附于宿主细胞是感染过程的第一步。这些细菌可利用其外膜蛋白黏附于各种生物和非生物表面。三聚体自转运黏附素(TAAs)是长度和结构域复杂性各异的模块化同三聚体。它们是构成Vc型分泌途径的一个多样且广泛存在的基因家族。这些黏附素已被确定为……中的毒力因子。迄今为止,尚未对该属中的三聚体自转运蛋白家族进行全面详尽的研究。在本研究中,使用了各种生物信息学工具,以对该属中这个蛋白质家族的序列和结构提供新的进化见解。为此,构建了来自……基因组的所有三聚体自转运蛋白的数据集。分析包括但不限于序列比对、系统发育树构建、基于密码子的选择测试、序列聚类以及结构(一级到四级)预测。对该数据集的批量分析表明,在整个群体中存在一些结构域。选择来自……2308基因组的BatA作为参考来描述这些结构域的特征。此外,我们通过分子动力学评估研究了观察到的蛋白质结构刚性和弹性的结构基础,这使我们推断随机漂变导致了该属中三聚体自转运蛋白基因的非适应性进化。值得注意的是,这些修饰在整个属中都有发生,且不受基因传递的干扰。