肺炎克雷伯菌耐药机制和毒力因子研究进展

Advances in mechanisms of resistance and virulence factors of Klebsiella pneumoniae

肺炎克雷伯菌是寄生于人和动物的皮肤、呼吸道、肠道等处的机会致病菌,具有较高的致病性,常引起呼吸系统、泌尿系统等感染,甚至出现败血症、脑炎等。肺炎克雷伯菌可分为经典肺炎克雷伯菌(cKP)与高毒力肺炎克雷伯菌(hvKP),hvKP能导致更严重、散播性更强的感染。目前,肺炎克雷伯菌的耐药性增强,耐药菌株的流行呈全球性和多样化的趋势,已引发关注。除了外排泵,肺炎克雷伯菌对抗菌药产生耐药性的机制有很多种,并且可以随着可移动遗传元件快速传播。本文详细阐述了肺炎克雷伯菌对β-内酰胺类、喹诺酮类、氨基糖苷类、替加环素、多黏菌素等抗菌药物的耐药机制。肺炎克雷伯菌的毒力因子多样,包括荚膜、脂多糖、黏附素、PEG-344、铁载体(肠杆菌素、沙门菌素、耶尔森菌素、气杆菌素)、外膜蛋白等。目前,对肺炎克雷伯菌的致病性和耐药性的研究越来越深入,在治疗方面也不断推进,主要的策略包括老药新用、纳米化抗菌药、新型抗菌药研发、噬菌体疗法、抗体疗法等。对肺炎克雷伯菌耐药机制、毒力因子进行详细、全面的综述,可为肺炎克雷伯菌的防控和临床用药提供参考。肺炎克雷伯菌的生物学特性、精准诊断、与宿主不同组织细胞的互作机制、宿主免疫应答机制等方面仍需深入研究。

Klebsiella pneumoniae(K.pneumoniae)is an opportunistic pathogen where parasitizes the skin,respiratory and intestine of humans and other animals,and it has high-grade pathogenic,with the urinary tract,respiratory system,or bloodstream,even septicemia and meningoencephalitis.K.pneumoniae is classified into classical K.pneumoniae(cKP)and hypervirulent K.pneumoniae(hvKP),which can cause more severe and aggressive infection.Currently,the drug resistance on K.pneumoniae has shown an obvious upward trend,global and diverse epidemiological trends have attracted widespread attention.There are many mechanisms through which K.pneumoniae develop resistance to antimicrobial agents besides efflux pumps,and are capable of rapid spread with mobile genetic elements.The mechanisms of antibiotics resistance in K.pneumoniae,including toβ-lactams,quinolones,aminoglycosides,tigecycline and colistin,were described in detail in this paper.The virulence factors of K.pneumoniae include capsule,lipopolysaccharide,adhesin,PEG-344,siderophores(enterobactin,salmochelin,yersiniabactin,and aerobactin)and outer membrane proteins.The research on K.pneumoniae antimicrobial resistance and pathogenicity has become more and more in depth,and treatment is continuously advancing.The main strategies involve new uses of old drugs,nano-antibiotics,novel antimicrobial research and development,bacteriophage therapy,and antibody therapy.This review provides a systematic review of resistance mechanism and virulence factors of K.pneumoniae may be helpful as a reference for the prevention,control,and clinical treatment.Further researches of biological properties,precise diagnosis,the mechanism of interaction with host tissue cells and host immune response,and mechanisms of K.pneumoniae are still required.