The increase of infections caused by multidrug-resistant bacteria, together with the loss of effectiveness of currently available antibiotics, represents one of the most serious threats to public health worldwide. The loss of human lives and the economic costs associated to the problem of the dissemination of antibiotic resistance require immediate action. Bacteria, known by their great genetic plasticity, are capable not only of mutating their genes to adapt to disturbances and environmental changes but also of acquiring new genes that allow them to survive in hostile environments, such as in the presence of antibiotics. One of the major mechanisms responsible for the horizontal acquisition of new genes (e.g., antibiotic resistance genes) is bacterial conjugation, a process mediated by mobile genetic elements such as conjugative plasmids and integrative conjugative elements. Conjugative plasmids harboring antibiotic resistance genes can be transferred from a donor to a recipient bacterium in a process that requires physical contact. After conjugation, the recipient bacterium not only harbors the antibiotic resistance genes but it can also transfer the acquired plasmid to other bacteria, thus contributing to the spread of antibiotic resistance. Conjugative plasmids have genes that encode all the proteins necessary for the conjugation to take place, such as the type IV coupling proteins (T4CPs) present in all conjugative plasmids. Type VI coupling proteins constitute a heterogeneous family of hexameric ATPases that use energy from the ATP hydrolysis for plasmid transfer. Taking into account their essential role in bacterial conjugation, T4CPs are attractive targets for the inhibition of bacterial conjugation and, concomitantly, the limitation of antibiotic resistance dissemination. This review aims to compile present knowledge on T4CPs as a starting point for delving into their molecular structure and functioning in future studies. Likewise, the scientific literature on bacterial conjugation inhibitors has been reviewed here, in an attempt to elucidate the possibility of designing T4CP-inhibitors as a potential solution to the dissemination of multidrug-resistant bacteria.

多重耐药细菌引起的感染增加，加上现有抗生素的有效性丧失，是全球公共卫生面临的最严重威胁之一。与抗生素耐药性传播问题相关的人员生命损失和经济损失需要立即采取行动。细菌以其巨大的遗传可塑性而闻名，不仅能够突变其基因以适应干扰和环境变化，而且还能够获得新的基因，使它们能够在恶劣的环境中生存，例如在抗生素存在的情况下。负责新基因水平获取的主要机制之一（例如..，抗生素抗性基因）是细菌接合，这是由接合质粒和整合接合元件等可移动遗传元件介导的过程。含有抗生素抗性基因的接合质粒可以在需要物理接触的过程中从供体细菌转移到受体细菌。接合后，受体细菌不仅携带抗生素抗性基因，还可以将获得的质粒转移给其他细菌，从而促进抗生素抗性的传播。接合质粒具有编码发生接合所需的所有蛋白质的基因，例如所有接合质粒中存在的 IV 型偶联蛋白 (T4CP)。VI 型偶联蛋白构成了六聚体 ATP 酶的异质家族，它们利用 ATP 水解产生的能量进行质粒转移。考虑到它们在细菌接合中的重要作用，T4CP 是抑制细菌接合以及限制抗生素耐药性传播的有吸引力的靶标。本综述旨在汇编有关 T4CP 的现有知识，作为深入研究其分子结构和未来研究功能的起点。同样，本文回顾了有关细菌结合抑制剂的科学文献，试图阐明设计 T4CP 抑制剂作为多重耐药细菌传播的潜在解决方案的可能性。