摘要
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。
Antibiotic resistance has impeded the cure of bacterial infections as evident with ESKAPE pathogens which include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. Multidrug resistance （MDR） in P. aeruginosa is largely attributable to the multiple multidrug efflux pumps such as MexAB-OprM and MexXY belonging to the resistance- nodulation-division （RND） superfamily. Since the discovery of RND pumps two decades ago, our ever-expanding understanding of these pumps has provided substantial insights into the clinical significance, structure, assembly, mechanism, regulation and inhibition of RND pumps in P aeruginosa. Multidrug effiux pumps not only contribute to MDR of clinical relevance, but also are involved in other functions including stress response s and virulence. Antibiotic development is continually challenged in discovering molecules that can bypass this efflux mechanism or be used as effective efflux pump inhibitors in the combination with antipseudomonal drugs. This aIticle aims at providing an update on many of the aforementioned advances achieved in the last decade after the publication of a previous review on the same topic in 2003 in this journal. These studies have again compellingly demonstrated both the importance and urgency of the prudent use of antibiotic agents in all settings to avert a post-antibiotic era.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2012年第7期481-500,共20页
Chinese Journal of Antibiotics
作者简介
作者简介：李显志，男，博士，药物评审主管，从事抗菌药物人类安全性评价与耐药性研究，E—mail：xianthi_li@yahoo．com
