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细菌抗生素耐药性严重地威胁着感染性疾病的治疗,如常见于ESKAPE病原菌(即肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠道杆菌属)。铜绿假单胞菌的多重药物耐药性主要在于该菌具有多重药物外排泵如MexAB-OprM和MexXY,后者属于耐药结节细胞分化(RND)家族转运体。自20年前发现RND外排泵后,现已对这些外排泵的临床意义、结构与组装、外排机制、表达调控与抑制等有了深入的认识。药物外排泵不仅介导了具有临床重要意义的多重耐药性,而且参与了其他细胞功能如恶劣环境下(包括存在抗菌药物时)的应激反应和致病性等。研究开发不受外排泵明显作用的抗菌药物或外排泵抑制剂以便与作为外排泵底物的抗铜绿假单胞菌抗生素联合应用仍然是新药研发所面临的一大挑战。本文旨在回顾讨论作者于2003年在本刊所发表的相关综述后上述多个方面过去10年的研究进展。这些研究再次清楚显示全面合理控制各类抗生素使用的重要性和紧迫性以避免后抗生素时代的来临。
Bacterial antibiotic resistance is a serious threat to the treatment of infectious diseases, as is common in ESKAPE pathogens (ie Enterococcus, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and enteric Bacillus). The multidrug resistance of Pseudomonas aeruginosa mainly consists of multiple drug efflux pumps such as MexAB-OprM and MexXY, the latter belonging to the RND family of drug-resistant transporters. Since the RND efflux pump was discovered 20 years ago, the clinical significance, structure and assembly, efflux mechanism, expression regulation and repression of these efflux pumps have been well recognized. Drug efflux pumps not only mediate clinically important multidrug resistance but also stress responses and pathogenicity in other cellular functions such as harsh environments (including the presence of antimicrobials). Research and development of antimicrobial drugs or efflux pump inhibitors that are not significantly affected by efflux pumps in combination with anti-Pseudomonas aeruginosa antibiotics as an efflux pump remains a major challenge for drug discovery. The purpose of this paper is to review the research progress of the above aspects in the past 10 years after the author reviewed the related articles published in this issue in 2003. These studies once again clearly demonstrate the importance and urgency of comprehensively and rationally controlling the use of various antibiotics to avoid the post-antibiotic era.