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细菌基因组可塑性的驱动因素及其在病原体毒力、持久性和耐药性中所起的作用。

Drivers of bacterial genomes plasticity and roles they play in pathogen virulence, persistence and drug resistance.

作者信息

Patel Seema

机构信息

Bioinformatics and Medical Informatics Research Center, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182, USA.

出版信息

Infect Genet Evol. 2016 Nov;45:151-164. doi: 10.1016/j.meegid.2016.08.030. Epub 2016 Aug 30.

Abstract

Despite the advent of next-generation sequencing (NGS) technologies, sophisticated data analysis and drug development efforts, bacterial drug resistance persists and is escalating in magnitude. To better control the pathogens, a thorough understanding of their genomic architecture and dynamics is vital. Bacterial genome is extremely complex, a mosaic of numerous co-operating and antagonizing components, altruistic and self-interested entities, behavior of which are predictable and conserved to some extent, yet largely dictated by an array of variables. In this regard, mobile genetic elements (MGE), DNA repair systems, post-segregation killing systems, toxin-antitoxin (TA) systems, restriction-modification (RM) systems etc. are dominant agents and horizontal gene transfer (HGT), gene redundancy, epigenetics, phase and antigenic variation etc. processes shape the genome. By illegitimate recombinations, deletions, insertions, duplications, amplifications, inversions, conversions, translocations, modification of intergenic regions and other alterations, bacterial genome is modified to tackle stressors like drugs, and host immune effectors. Over the years, thousands of studies have investigated this aspect and mammoth amount of insights have been accumulated. This review strives to distillate the existing information, formulate hypotheses and to suggest directions, that might contribute towards improved mitigation of the vicious pathogens.

摘要

尽管新一代测序(NGS)技术问世,数据分析和药物研发工作也日益精细,但细菌耐药性问题依然存在且愈演愈烈。为了更好地控制病原体,深入了解其基因组结构和动态变化至关重要。细菌基因组极其复杂,是众多协同与拮抗成分、利他与利己实体的镶嵌体,其行为在一定程度上具有可预测性和保守性,但在很大程度上受一系列变量的支配。在这方面,移动遗传元件(MGE)、DNA修复系统、后分离杀伤系统、毒素-抗毒素(TA)系统、限制修饰(RM)系统等是主要因素,水平基因转移(HGT)、基因冗余、表观遗传学、相位和抗原变异等过程塑造了基因组。通过非法重组、缺失、插入、重复、扩增、倒位、转换、易位、基因间区域修饰及其他改变,细菌基因组得以修饰,以应对诸如药物和宿主免疫效应器等应激源。多年来,数以千计的研究对这一方面进行了调查,并积累了大量见解。本综述旨在提炼现有信息、提出假设并给出方向,以期为更好地应对这些恶性病原体做出贡献。

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