摘要

      细菌的抗微生物耐药性（AMR）是一个影响人类、动物和环境的重要全球健康问题。AMR被认为是“全球同一健康”的主要组成部分之一。任何一个环节滥用/过度使用抗生素都会影响其他环节的完整性。在抗生素选择性压力的存在下，细菌倾向于发展几种防御机制，包括细菌外膜的结构变化、酶促过程、基因上调、突变、适应性抗性和生物膜形成。移动遗传元件（MGE）的几个组成部分在AMR的传播中发挥着重要作用。这些成分中的每一种都有一种特定的功能，无论任何抗生素压力如何，都能持续很长时间。整合和偶联元件（ICEs）、插入序列元件（IS）和转座子在不同的遗传主链上携带抗微生物耐药性基因（ARGs）。ARGs的成功转移取决于质粒的种类、调节子、ISs的接近程度和重组系统的类型。此外，噬菌体-细菌网络在ARGs的传播中发挥着重要作用，尤其是在来自动物来源的环境和食物的细菌中。细菌的其他几个功能属性也被成功地修饰以获得ARGs。其中包括外排泵、毒素-抗毒素系统、调节性小RNA、五磷酸鸟苷信号传导、群体感应、双组分系统和集群规则间隔短回文重复序列（CRISPR）系统。细菌的代谢和毒力状态也与一系列遗传和表型抗性机制有关。尽管有大量关于AMR的信息，但人们对选择压力和上述几个组件之间的网络关联知之甚少。了解病原体如何抵抗和调节ARGs以响应抗菌药物，有助于控制耐药性的发展。在这里，我们概述了细菌病原体中AMR的遗传网络和调节的重要性。Antimicrobial resistance (AMR) in bacteria is an important global health problem affecting humans, animals, and the environment. AMR is considered as one of the major components in the “global one health”. Misuse/overuse of antibiotics in any one of the segments can impact the integrity of the others. In the presence of antibiotic selective pressure, bacteria tend to develop several defense mechanisms, which include structural changes of the bacterial outer membrane, enzymatic processes, gene upregulation, mutations, adaptive resistance, and biofilm formation. Several components of mobile genetic elements (MGEs) play an important role in the dissemination of AMR. Each one of these components has a specific function that lasts long, irrespective of any antibiotic pressure. Integrative and conjugative elements (ICEs), insertion sequence elements (ISs), and transposons carry the antimicrobial resistance genes (ARGs) on different genetic backbones. Successful transfer of ARGs depends on the class of plasmids, regulons, ISs proximity, and type of recombination systems. Additionally, phage-bacterial networks play a major role in the transmission of ARGs, especially in bacteria from the environment and foods of animal origin. Several other functional attributes of bacteria also get successfully modified to acquire ARGs. These include efflux pumps, toxin-antitoxin systems, regulatory small RNAs, guanosine pentaphosphate signaling, quorum sensing, two-component system, and clustered regularly interspaced short palindromic repeats (CRISPR) systems. The metabolic and virulence state of bacteria is also associated with a range of genetic and phenotypic resistance mechanisms. In spite of the availability of a considerable information on AMR, the network associations between selection pressures and several of the components mentioned above are poorly understood. Understanding how a pathogen resists and regulates the ARGs in response to antimicrobials can help in controlling the development of resistance. Here, we provide an overview of the importance of genetic network and regulation of AMR in bacterial pathogens.

https://www.frontiersin.org/articles/10.3389/fcimb.2022.952491/full?utm_source=dlvr.it&utm_medium=twitter