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.

临床相关细菌含有可移动遗传元件(MGES)，用于在相容细胞之间有效地洗牌遗传物质。由于MGES编码毒力和抗生素抗性基因(ARGs)，具有将良性细菌转化为强毒或耐药病原菌的潜力，因此MGES在细菌进化和毒力及其转移机制中的影响已被广泛研究。相反，尽管染色体上也含有大量的毒力和ARG，与经典的MGES不相关，但由于染色体基因水平转移的频率相对较低，这些基因对新细菌和抗性克隆的出现的影响被认为是次要的。在这个研究计划中，我们挑战了这一经典观点，并提出染色体基因的移动性超过MGES。虽然运动组的概念是明确的，但我们在这里提出，鉴于第三种也是最强大的噬菌体介导的DNA转移模式的发现：侧向转导(LT)，细菌中更广泛的遗传迁移率的概念需要重新定义。我们预计，当这一机制的全部影响被考虑时，可移植的MGES和不活动的染色体的经典二分法将不再适用，因为染色体基因可以以等于或高于MGES的惊人的高频率被动员。我们建议重新评估移动体和染色体在水平基因转移中的相对影响，这将挑战既定的教条。了解为什么染色体需要以如此高的频率被动员，以及这种惊人的流动性的后果是什么，这是至关重要的。这些问题的答案将为细菌进化和临床传染病提供全新的概念。我们的结果也将为耐药和毒力强的细菌病原体如何不断出现提供线索，并对人类和动物健康产生重要后果。