Redefining mobility in bacterial genetics and its impact on infectious disease.

重新定义细菌遗传学的流动性及其对传染病的影响。

• 批准号: MR/X020223/1
• 负责人: Jose R Penades
• 金额: $ 258.47万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX020223%2F1
• 关键词: Redefining; mobility; bacterial; genetics; its

Clinically relevant bacteria harbour mobile genetic elements (MGEs) for the efficient shuffling of genetic material between compatible cells. Since MGEs encode virulence and antibiotic resistance genes (ARGs), with the potential to transform a benign bacterium into a virulent or drug resistant pathogen, the impact of MGEs in bacterial evolution and virulence, and their mechanisms of transfer, have been extensively studied. By contrast, although chromosomes also contain an impressive arsenal of virulence and ARGs not associated with classical MGEs, the impact of these genes on the emergence of novel bacterial and resistant clones has been considered of lesser importance due to the relatively low frequency of horizontal transfer of chromosomal genes.In this programme of research, we challenge this classical view and propose that the mobility of chromosomal genes exceeds that of the MGEs. While the mobilome concept is well defined, we propose here that the broader concept of genetic mobility in bacteria requires redefinition, in the light of the discovery of the third and most powerful mode of phage-mediated DNA transfer: lateral transduction (LT). We anticipate that when the full impact of this mechanism is considered, the classical dichotomy of portable MGEs and immobile chromosomes will no longer hold true because chromosomal genes can be mobilised at astonishingly high frequencies equal to or higher than MGEs. We propose a re-evaluation of the relative impact of the mobilome and the chromosome on horizontal gene transfer, that will challenge the established dogma. It is essential to understand why chromosomes need to be mobilised at such high frequencies, and what are the consequences of such astonishing mobility. The answer to these questions will provide brand new concepts central to bacterial evolution and clinical infectious disease. Our results will also provide light on how resistant and virulent bacterial pathogens continually emerge, with important consequences for human and animal health.

临床相关细菌具有可移动遗传元件（MGE），可在相容细胞之间有效地改组遗传物质。由于 MGE 编码毒力和抗生素抗性基因 (ARG)，有可能将良性细菌转化为毒力或耐药病原体，因此 MGE 对细菌进化和毒力的影响及其转移机制已得到广泛研究。相比之下，尽管染色体还含有令人印象深刻的毒力库和与经典 MGE 无关的 ARG，但由于水平转移的频率相对较低，这些基因对新型细菌和耐药克隆出现的影响被认为不太重要。染色体基因。在本研究项目中，我们挑战了这一经典观点，并提出染色体基因的迁移率超过了 MGE。虽然移动组概念已经明确定义，但我们在此提出，鉴于噬菌体介导的 DNA 转移的第三种也是最强大的模式：横向转导 (LT) 的发现，需要重新定义更广泛的细菌遗传移动性概念。我们预计，当考虑到这种机制的全面影响时，便携式 MGE 和固定染色体的经典二分法将不再成立，因为染色体基因可以以等于或高于 MGE 的惊人高频率被动员。我们建议重新评估移动组和染色体对水平基因转移的相对影响，这将挑战既定的教条。有必要了解为什么染色体需要以如此高的频率移动，以及这种惊人的移动会产生什么后果。这些问题的答案将为细菌进化和临床传染病提供全新的核心概念。我们的研究结果还将揭示耐药性和剧毒细菌病原体如何不断出现，对人类和动物健康产生重要影响。