School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom.
Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-Consejo Superior de Investigaciones Científicas, Santander, Spain.
Microbiol Spectr. 2018 Jan;6(1). doi: 10.1128/microbiolspec.MTBP-0015-2016.
Conjugative plasmids are the main carriers of transmissible antibiotic resistance (AbR) genes. For that reason, strategies to control plasmid transmission have been proposed as potential solutions to prevent AbR dissemination. Natural mechanisms that bacteria employ as defense barriers against invading genomes, such as restriction-modification or CRISPR-Cas systems, could be exploited to control conjugation. Besides, conjugative plasmids themselves display mechanisms to minimize their associated burden or to compete with related or unrelated plasmids. Thus, FinOP systems, composed of FinO repressor protein and FinP antisense RNA, aid plasmids to regulate their own transfer; exclusion systems avoid conjugative transfer of related plasmids to the same recipient bacteria; and fertility inhibition systems block transmission of unrelated plasmids from the same donor cell. Artificial strategies have also been designed to control bacterial conjugation. For instance, intrabodies against R388 relaxase expressed in recipient cells inhibit plasmid R388 conjugative transfer; pIII protein of bacteriophage M13 inhibits plasmid F transmission by obstructing conjugative pili; and unsaturated fatty acids prevent transfer of clinically relevant plasmids in different hosts, promoting plasmid extinction in bacterial populations. Overall, a number of exogenous and endogenous factors have an effect on the sophisticated process of bacterial conjugation. This review puts them together in an effort to offer a wide picture and inform research to control plasmid transmission, focusing on Gram-negative bacteria.
结合性质粒是可传播抗生素耐药性（AbR）基因的主要载体。因此，提出了控制质粒传播的策略，作为防止 AbR 传播的潜在解决方案。细菌用来抵御入侵基因组的天然防御屏障机制，如限制修饰或 CRISPR-Cas 系统，可以被利用来控制 conjugation。此外，结合性质粒本身也具有最小化其相关负担或与相关或不相关质粒竞争的机制。因此，由 FinO 阻遏蛋白和 FinP 反义 RNA 组成的 FinOP 系统有助于质粒调节自身的转移；排除系统可避免相关质粒在同一受体细菌中的接合转移；而生育抑制系统则阻止同一供体细胞中非相关质粒的传播。还设计了人工策略来控制细菌接合。例如，在受体细胞中表达的针对 R388 松弛酶的内抗体抑制质粒 R388 的接合转移；噬菌体 M13 的 pIII 蛋白通过阻碍接合性菌毛来抑制质粒 F 的传递；不饱和脂肪酸可防止不同宿主中临床相关质粒的转移，促进细菌种群中质粒的灭绝。总的来说，许多外源性和内源性因素都会影响细菌接合的复杂过程。本综述将它们放在一起，以期提供一个广泛的画面，并为控制质粒传播的研究提供信息，重点是革兰氏阴性菌。
