Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India.
Collaborative Research Centre of Okayama University for Infectious Diseases at ICMR- National Institute of Cholera and Enteric Diseases, Kolkata, India.
Front Cell Infect Microbiol. 2022 Nov 23;12:952491. doi: 10.3389/fcimb.2022.952491. eCollection 2022.
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.
细菌的抗微生物药物耐药性 (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。任何一个环节对抗生素的滥用/过度使用都会影响其他环节的完整性。在抗生素选择压力下，细菌往往会发展出几种防御机制，包括细菌外膜的结构变化、酶过程、基因上调、突变、适应性耐药和生物膜形成。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。这些组成部分中的每一个都具有特定的功能，并且持续时间长，不受任何抗生素压力的影响。整合子-转座子元件 (ICEs)、插入序列元件 (ISs) 和转座子在不同的遗传背景上携带抗微生物药物耐药基因 (ARGs)。ARGs 的成功转移取决于质粒的类别、调控子、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 的传播中起着主要作用，特别是在环境和动物源性食品中的细菌中。细菌的其他几个功能属性也成功地被修饰以获得 ARGs。这些包括外排泵、毒素-抗毒素系统、调节性小 RNA、鸟苷五磷酸信号、群体感应、双组分系统和成簇规则间隔短回文重复 (CRISPR) 系统。细菌的代谢和毒力状态也与一系列遗传和表型耐药机制有关。尽管已经有了相当多的关于 AMR 的信息，但对选择压力与上述提到的多个组成部分之间的网络关联知之甚少。了解病原体如何抵抗和调节 ARGs 以对抗抗生素有助于控制耐药性的发展。在这里，我们概述了遗传网络的重要性和细菌病原体中 AMR 的调控。
