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

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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.