Department of Biology, Barnard College, New York, NY, USA.
Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Mol Syst Biol. 2021 Mar;17(3):e9913. doi: 10.15252/msb.20209913.
Plasmid conjugation is a major mechanism responsible for the spread of antibiotic resistance. Plasmid fitness costs are known to impact long-term growth dynamics of microbial populations by providing plasmid-carrying cells a relative (dis)advantage compared to plasmid-free counterparts. Separately, plasmid acquisition introduces an immediate, but transient, metabolic perturbation. However, the impact of these short-term effects on subsequent growth dynamics has not previously been established. Here, we observed that de novo transconjugants grew significantly slower and/or with overall prolonged lag times, compared to lineages that had been replicating for several generations, indicating the presence of a plasmid acquisition cost. These effects were general to diverse incompatibility groups, well-characterized and clinically captured plasmids, Gram-negative recipient strains and species, and experimental conditions. Modeling revealed that both fitness and acquisition costs modulate overall conjugation dynamics, validated with previously published data. These results suggest that the hours immediately following conjugation may play a critical role in both short- and long-term plasmid prevalence. This time frame is particularly relevant to microbiomes with high plasmid/strain diversity considered to be hot spots for conjugation.
质粒接合是导致抗生素耐药性传播的主要机制。已知质粒适应性成本通过为携带质粒的细胞相对于无质粒的细胞提供相对(不利)优势,从而影响微生物种群的长期生长动态。另外,质粒的获得会立即但短暂地引起代谢干扰。然而,这些短期效应对后续生长动态的影响以前尚未确定。在这里,我们观察到与已经复制了几代的谱系相比,从头开始的转导子生长明显较慢和/或总体延长了迟滞时间,表明存在质粒获得成本。这些效应对于不同的不相容群、特征明确且临床上捕获的质粒、革兰氏阴性受体菌株和种以及实验条件都是普遍存在的。建模表明适应性和获得性成本都调节整体接合动力学,这与之前发表的数据相吻合。这些结果表明,接合后立即的几个小时可能在短期和长期质粒流行中都起着关键作用。这个时间框架对于具有高质粒/菌株多样性的微生物组特别重要,因为它们被认为是接合的热点。