Baffert Yannick, Fraikin Nathan, Makhloufi Yasmine, Baltenneck Julie, Val Marie-Eve, Dedieu-Berne Annick, Degosserie Jonathan, Iorga Bogdan I, Bogaerts Pierre, Gueguen Erwan, Lesterlin Christian, Bigot Sarah
Microbiologie Moléculaire et Biochimie Structurale (MMSB), Université Lyon 1, CNRS, Inserm, UMR5086, Lyon, France.
Microbiologie Adaptation et Pathogénie (MAP), Université Lyon 1, INSA de Lyon, CNRS, UMR 5240, Villeurbanne, France.
Nat Commun. 2025 Aug 19;16(1):7734. doi: 10.1038/s41467-025-62404-7.
Conjugative plasmids are the main drivers of antibiotic resistance dissemination contributing to the emergence and extensive spread of multidrug resistance clinical bacterial pathogens. pOXA-48 plasmids, belonging to the IncL group, emerge as the primary vehicle for carbapenem resistance in Enterobacteriaceae. Despite the problematic prevalence of pOXA-48, most research focus on epidemiology and genomics, leaving gaps in our understanding of the mechanisms behind its propagation. In this study, we use a transposon sequencing approach to identify genetic elements critical for plasmid stability, replication, and conjugative transfer. Our results identify a novel type I toxin-antitoxin system, uncharacterized essential maintenance factors, and components of the type IV secretion system and regulatory elements crucial for conjugation. This study advances our understanding of pOXA-48 biology, providing key insights into the genetic factors underlying its successful maintenance and spread in bacterial populations.
接合质粒是抗生素耐药性传播的主要驱动因素，导致多重耐药临床细菌病原体的出现和广泛传播。属于IncL组的pOXA - 48质粒成为肠杆菌科中碳青霉烯耐药性的主要载体。尽管pOXA - 48普遍存在问题，但大多数研究集中在流行病学和基因组学上，在我们对其传播背后机制的理解上留下了空白。在本研究中，我们使用转座子测序方法来鉴定对质粒稳定性、复制和接合转移至关重要的遗传元件。我们的结果鉴定出一种新型I型毒素 - 抗毒素系统、未表征的必需维持因子、IV型分泌系统的组成部分以及对接合至关重要的调控元件。这项研究推进了我们对pOXA - 48生物学的理解，为其在细菌群体中成功维持和传播的潜在遗传因素提供了关键见解。
