关键词: ESBL Escherichia coli UPEC antibiotic resistance efflux pump

Mesh : Humans Escherichia coli / genetics Escherichia coli Infections / drug therapy Microbial Sensitivity Tests Anti-Bacterial Agents / pharmacology therapeutic use beta-Lactamases / genetics Drug Resistance, Microbial

来  源:   DOI:10.3389/fcimb.2024.1387497   PDF(Pubmed)

Abstract:
The dissemination of antibiotic resistance in Escherichia coli poses a significant threat to public health worldwide. This review provides a comprehensive update on the diverse mechanisms employed by E. coli in developing resistance to antibiotics. We primarily focus on pathotypes of E. coli (e.g., uropathogenic E. coli) and investigate the genetic determinants and molecular pathways that confer resistance, shedding light on both well-characterized and recently discovered mechanisms. The most prevalent mechanism continues to be the acquisition of resistance genes through horizontal gene transfer, facilitated by mobile genetic elements such as plasmids and transposons. We discuss the role of extended-spectrum β-lactamases (ESBLs) and carbapenemases in conferring resistance to β-lactam antibiotics, which remain vital in clinical practice. The review covers the key resistant mechanisms, including: 1) Efflux pumps and porin mutations that mediate resistance to a broad spectrum of antibiotics, including fluoroquinolones and aminoglycosides; 2) adaptive strategies employed by E. coli, including biofilm formation, persister cell formation, and the activation of stress response systems, to withstand antibiotic pressure; and 3) the role of regulatory systems in coordinating resistance mechanisms, providing insights into potential targets for therapeutic interventions. Understanding the intricate network of antibiotic resistance mechanisms in E. coli is crucial for the development of effective strategies to combat this growing public health crisis. By clarifying these mechanisms, we aim to pave the way for the design of innovative therapeutic approaches and the implementation of prudent antibiotic stewardship practices to preserve the efficacy of current antibiotics and ensure a sustainable future for healthcare.
摘要:
大肠杆菌中抗生素耐药性的传播对全球公共卫生构成重大威胁。这篇综述提供了大肠杆菌在开发抗生素耐药性中所采用的多种机制的全面更新。我们主要关注大肠杆菌的致病型(例如,尿路致病性大肠杆菌),并研究赋予耐药性的遗传决定因素和分子途径,揭示了特征明确和最近发现的机制。最普遍的机制仍然是通过水平基因转移获得抗性基因,由移动遗传元件如质粒和转座子促进。我们讨论了超广谱β-内酰胺酶(ESBLs)和碳青霉烯酶在赋予β-内酰胺抗生素耐药性中的作用,这在临床实践中仍然至关重要。审查涵盖了关键的抵抗机制,包括:1)外排泵和孔蛋白突变,介导对广谱抗生素的抗性,包括氟喹诺酮类和氨基糖苷类;2)大肠杆菌采用的适应性策略,包括生物膜的形成,持久细胞的形成,和激活应激反应系统,承受抗生素压力;3)监管系统在协调耐药机制中的作用,提供对治疗干预的潜在目标的见解。了解大肠杆菌中复杂的抗生素耐药机制网络对于制定有效的策略来应对这种日益严重的公共卫生危机至关重要。通过澄清这些机制,我们的目标是为创新治疗方法的设计和审慎抗生素管理实践的实施铺平道路,以保持当前抗生素的功效,并确保医疗保健的可持续未来。
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