Survival and Evolution of a Large Multidrug Resistance Plasmid in New Clinical Bacterial Hosts.
Survival and Evolution of a Large Multidrug Resistance Plasmid in New Clinical Bacterial Hosts.
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DOI：
10.1093/molbev/msw163
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发表时间：
2016-11
影响因子：
10.7
通讯作者：
Sommer MO
中科院分区：
文献类型：
--
作者：
Porse A;Schønning K;Munck C;Sommer MO
大接合质粒是细菌进化的重要驱动力，并显著促进抗生素耐药性的传播。虽然质粒携带的多药耐药性被认为是现代医学的主要挑战之一，但对这些质粒在致病宿主中形成进化的适应力知之甚少。在这里，我们研究质粒宿主的适应性转移后，73 kb的接合性多药耐药质粒的肺炎克雷伯菌和大肠杆菌的幼稚临床分离株。我们使用实验进化、数学建模和群体测序来表明，质粒的长期持续性和分子完整性受到构成宿主依赖性负担的25 kb质粒区域内多种因素的高度影响。在急诊在这里研究的大肠杆菌宿主中，通过IS26介导的从质粒骨架中删除昂贵区域，有效地扩大了质粒的宿主范围，很容易进化出改善的质粒稳定性。虽然这些适应也有利于质粒在幼稚K. pneumoniae宿主中，它们从未在该物种中观察到，表明差异进化性可以限制质粒适应的机会。虽然插入序列是众所周知的，以提供质粒的适应性性状，我们的研究结果表明，它们也发挥了重要作用，在质粒的进化，保持必要的可塑性，以减轻质粒宿主的约束。此外，观察到的进化策略一致遵循所有进化E。大肠杆菌谱系暴露了水平和垂直传播之间的权衡，这可能最终限制临床多药耐药质粒在这些宿主中的传播潜力。
Large conjugative plasmids are important drivers of bacterial evolution and contribute significantly to the dissemination of antibiotic resistance. Although plasmid borne multidrug resistance is recognized as one of the main challenges in modern medicine, the adaptive forces shaping the evolution of these plasmids within pathogenic hosts are poorly understood. Here we study plasmid–host adaptations following transfer of a 73 kb conjugative multidrug resistance plasmid to naïve clinical isolates of Klebsiella pneumoniae and Escherichia coli. We use experimental evolution, mathematical modelling and population sequencing to show that the long-term persistence and molecular integrity of the plasmid is highly influenced by multiple factors within a 25 kb plasmid region constituting a host-dependent burden. In the E. coli hosts investigated here, improved plasmid stability readily evolves via IS26 mediated deletions of costly regions from the plasmid backbone, effectively expanding the host-range of the plasmid. Although these adaptations were also beneficial to plasmid persistence in a naïve K. pneumoniae host, they were never observed in this species, indicating that differential evolvability can limit opportunities of plasmid adaptation. While insertion sequences are well known to supply plasmids with adaptive traits, our findings suggest that they also play an important role in plasmid evolution by maintaining the plasticity necessary to alleviate plasmid–host constrains. Further, the observed evolutionary strategy consistently followed by all evolved E. coli lineages exposes a trade-off between horizontal and vertical transmission that may ultimately limit the dissemination potential of clinical multidrug resistance plasmids in these hosts.
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影响因子：
4.5
作者：
Guynet C;Cuevas A;Moncalián G;de la Cruz F
通讯作者：
de la Cruz F
影响因子：
3.3
作者：
Dionisio, F;Conceiçao, IC;Gordo, I
通讯作者：
Gordo, I
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
17.1
作者：
Conlan S;Thomas PJ;Deming C;Park M;Lau AF;Dekker JP;Snitkin ES;Clark TA;Luong K;Song Y;Tsai YC;Boitano M;Dayal J;Brooks SY;Schmidt B;Young AC;Thomas JW;Bouffard GG;Blakesley RW;NISC Comparative Sequencing Program;Mullikin JC;Korlach J;Henderson DK;Frank KM;Palmore TN;Segre JA
通讯作者：
Segre JA
影响因子：
4.9
作者：
Curiao, Tania;Canton, Rafael;Coque, Teresa M.
通讯作者：
Coque, Teresa M.