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对 核心和获得基因组之间的基因组动态和相互作用的分子见解。

Molecular insights into the genome dynamics and interactions between core and acquired genomes of .

机构信息

Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad 121001, India.

South-East Asia Regional Office, World Health Organization, New Delhi 110002, India.

出版信息

Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23762-23773. doi: 10.1073/pnas.2006283117. Epub 2020 Sep 1.

Abstract

Bacterial species are hosts to horizontally acquired mobile genetic elements (MGEs), which encode virulence, toxin, antimicrobial resistance, and other metabolic functions. The bipartite genome of harbors sporadic and conserved MGEs that contribute in the disease development and survival of the pathogens. For a comprehensive understanding of dynamics of MGEs in the bacterial genome, we engineered the genome of and examined in vitro and in vivo stability of genomic islands (GIs), integrative conjugative elements (ICEs), and prophages. Recombinant vectors carrying the integration module of these GIs, ICE and CTXΦ, helped us to understand the efficiency of integrations of MGEs in the chromosome. We have deleted more than 250 acquired genes from 6 different loci in the chromosome and showed contribution of CTX prophage in the essentiality of SOS response master regulator LexA, which is otherwise not essential for viability in other bacteria, including In addition, we observed that the core genome-encoded RecA helps CTXΦ to bypass immunity and allow it to replicate in the host bacterium in the presence of similar prophage in the chromosome. Finally, our proteomics analysis reveals the importance of MGEs in modulating the levels of cellular proteome. This study engineered the genome of to remove all of the GIs, ICEs, and prophages and revealed important interactions between core and acquired genomes.

摘要

细菌物种是水平获得的移动遗传元件(MGE)的宿主,这些元件编码毒力、毒素、抗微生物药物抗性和其他代谢功能。harbor 的二分体基因组中存在散在和保守的 MGE,这些 MGE 有助于病原体的疾病发展和存活。为了全面了解细菌基因组中 MGE 的动态,我们对 进行了基因组工程改造,并在体外和体内研究了基因组岛(GI)、整合性 conjugative elements(ICEs)和 prophages 的稳定性。携带这些 GI、ICE 和 CTXΦ 整合模块的重组载体帮助我们了解了 MGE 在 染色体中的整合效率。我们已经从 染色体的 6 个不同基因座中删除了超过 250 个获得的基因,并表明 CTX 噬菌体在 SOS 反应主调控因子 LexA 的必需性中发挥作用,否则 LexA 在包括 在内的其他细菌中对于生存并非必需。此外,我们观察到核心基因组编码的 RecA 有助于 CTXΦ 绕过 免疫,并允许其在染色体中存在类似噬菌体时在宿主细菌中复制。最后,我们的蛋白质组学分析揭示了 MGE 在调节细胞蛋白质组水平方面的重要性。本研究对 进行了基因组工程改造,以去除所有的 GI、ICE 和 prophages,并揭示了核心和获得基因组之间的重要相互作用。

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