Université Paris Cité and Université Sorbonne Paris Nord, INSERM, IAME, Paris, France.
AP-HP, Laboratoire de Microbiologie Hygiène, Hôpital Louis Mourier, Colombes, France.
Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0055424. doi: 10.1128/aac.00554-24. Epub 2024 Aug 28.
It has been shown that an evolutionary tradeoff between vertical (host growth rate) and horizontal (plasmid conjugation) transmissions contributes to global plasmid fitness. As conjugative IncC plasmids are important for the spread of multidrug resistance (MDR), in a broad range of bacterial hosts, we investigated vertical and horizontal transmissions of two multidrug-resistant IncC plasmids according to their backbones and MDR-region rearrangements, upon plasmid entry into a new host. We observed plasmid genome deletions after conjugation in three diverse natural clinical strains, varying from null to high number depending on the plasmid, all occurring in the MDR region. The plasmid burden on bacterial fitness depended more on the strain background than on the structure of the MDR region, with deletions appearing to have no impact. Besides, we observed an increase in plasmid transfer rate, from ancestral host to new clinical recipient strains, when the IncC plasmid was rearranged. Finally, using a second set of conjugation experiments, we investigated the evolutionary tradeoff of the IncC plasmid during the critical period of plasmid establishment in K-12, by correlating the transfer rates of deleted or non-deleted IncC plasmids and their costs on the recipient strain. Plasmid deletions strongly improved conjugation efficiency with no negative growth effect. Our findings indicate that the flexibility of the MDR-region of the IncC plasmids can promote their dissemination, and provide diverse opportunities to capture new resistance genes. In a broader view, they suggest that the vertical-horizontal transmission tradeoff can be manipulated by the plasmid to improve its fitness.
已经表明，垂直（宿主生长率）和水平（质粒接合）传播之间的进化权衡有助于全局质粒适应性。由于可移动性 IncC 质粒对于广泛的细菌宿主中的多药耐药性（MDR）的传播很重要，因此我们根据质粒进入新宿主时的骨架和 MDR 区重排，研究了两个多药耐药性 IncC 质粒的垂直和水平传播。我们观察到在三个不同的天然临床菌株中，在接合后质粒基因组发生缺失，具体数量因质粒而异，所有缺失都发生在 MDR 区。质粒对细菌适应性的负担更多地取决于菌株背景，而不是 MDR 区的结构，缺失似乎没有影响。此外，当 IncC 质粒发生重排时，我们观察到质粒转移率从原始宿主增加到新的临床接受菌株。最后，通过使用第二组接合实验，我们通过比较缺失或非缺失 IncC 质粒的转移率及其对受体菌株的成本，研究了 IncC 质粒在 K-12 中质粒建立的关键时期的进化权衡。质粒缺失强烈提高了接合效率，而对受体菌株的生长没有负面影响。我们的研究结果表明，IncC 质粒的 MDR 区的灵活性可以促进其传播，并为捕获新的耐药基因提供了多种机会。从更广泛的角度来看，它们表明垂直-水平传播的权衡可以被质粒操纵，以提高其适应性。
