关键词: antibiotic stewardship antimicrobial resistance horizontal gene transfer integrons pathogenicity

来  源:   DOI:10.3389/fmicb.2023.1231938   PDF(Pubmed)

Abstract:
Antibiotic resistance development and pathogen cross-dissemination are both considered essential risks to human health on a worldwide scale. Antimicrobial resistance genes (AMRs) are acquired, expressed, disseminated, and traded mainly through integrons, the key players capable of transferring genes from bacterial chromosomes to plasmids and their integration by integrase to the target pathogenic host. Moreover, integrons play a central role in disseminating and assembling genes connected with antibiotic resistance in pathogenic and commensal bacterial species. They exhibit a large and concealed diversity in the natural environment, raising concerns about their potential for comprehensive application in bacterial adaptation. They should be viewed as a dangerous pool of resistance determinants from the \"One Health approach.\" Among the three documented classes of integrons reported viz., class-1, 2, and 3, class 1 has been found frequently associated with AMRs in humans and is a critical genetic element to serve as a target for therapeutics to AMRs through gene silencing or combinatorial therapies. The direct method of screening gene cassettes linked to pathogenesis and resistance harbored by integrons is a novel way to assess human health. In the last decade, they have witnessed surveying the integron-associated gene cassettes associated with increased drug tolerance and rising pathogenicity of human pathogenic microbes. Consequently, we aimed to unravel the structure and functions of integrons and their integration mechanism by understanding horizontal gene transfer from one trophic group to another. Many updates for the gene cassettes harbored by integrons related to resistance and pathogenicity are extensively explored. Additionally, an updated account of the assessment of AMRs and prevailing antibiotic resistance by integrons in humans is grossly detailed-lastly, the estimation of AMR dissemination by employing integrons as potential biomarkers are also highlighted. The current review on integrons will pave the way to clinical understanding for devising a roadmap solution to AMR and pathogenicity. Graphical AbstractThe graphical abstract displays how integron-aided AMRs to humans: Transposons capture integron gene cassettes to yield high mobility integrons that target res sites of plasmids. These plasmids, in turn, promote the mobility of acquired integrons into diverse bacterial species. The acquisitions of resistant genes are transferred to humans through horizontal gene transfer.
摘要:
抗生素耐药性发展和病原体交叉传播都被认为是全球范围内对人类健康的基本风险。抗菌素耐药基因(AMR)是获得性的,表达,传播,主要通过整合子进行交易,能够将基因从细菌染色体转移到质粒并通过整合酶整合到目标致病宿主的关键参与者。此外,整合子在传播和组装与致病性和共生细菌中的抗生素抗性相关的基因中起着核心作用。它们在自然环境中表现出巨大而隐蔽的多样性,引起人们对它们在细菌适应中的综合应用潜力的担忧。从“一个健康”方法来看,它们应被视为一个危险的抵抗决定因素池。\“在报告的三类文献中,即。,已经发现1类、2类和3类,1类在人类中经常与AMR相关,并且是作为通过基因沉默或组合疗法治疗AMR的靶标的关键遗传元件。筛选与整合子所具有的发病机理和抗性相关的基因盒的直接方法是评估人类健康的新方法。在过去的十年里,他们目睹了与人类病原微生物的药物耐受性增加和致病性上升相关的整合子相关基因盒的调查。因此,我们旨在通过了解从一个营养类群到另一个营养类群的水平基因转移来揭示整合子的结构和功能及其整合机制。广泛探索了与抗性和致病性相关的整合子所携带的基因盒的许多更新。此外,最后,对人类体内AMR和整合子对抗生素耐药性的评估进行了更新,还强调了通过使用整合子作为潜在生物标志物来估计AMR传播的方法.当前对整合子的审查将为临床理解铺平道路,以设计针对AMR和致病性的路线图解决方案。图形摘要图形摘要显示了整合子辅助AMR对人类的作用:转座子捕获整合子基因盒,以产生靶向质粒res位点的高迁移率整合子。这些质粒,反过来,促进获得的整合子迁移到不同的细菌物种。抗性基因的获得通过水平基因转移转移到人类。
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