艰难类梭菌耐药机制及其适应性代价的研究进展

Advance in antimicrobial resistance mechanisms and fitness cost of Clostridioides difficile

艰难类梭菌是一种革兰阳性、产芽胞的专性厌氧菌,是抗菌药物相关性腹泻最常见的病原菌。近年来,随着抗菌药物的广泛应用,艰难类梭菌的耐药率不断攀升。获得抗性基因、药物靶点突变、生物膜生成以及代谢途径发生改变是艰难类梭菌产生耐药性的主要原因。此外,耐药艰难类梭菌的适应性代价较低,即使在缺乏抗菌药物选择压力的环境中仍然可维持耐药性状,促使多重耐药菌株的出现及流行,为抗菌药物治疗埋下了巨大隐患。本文对艰难类梭菌的耐药机制及其适应性代价进行综述,旨在为减少耐药性、开发新疗法提供理论参考。

Clostridioes difficile is a Gram-positive,obligate anaerobic,spore-forming bacterium,and the main cause of hospital-associated diarrhea.In recent years,with the widespread use of antibiotics,the resistance rate of C.difficile has been increasing.Resistance to multiple antibiotics is a common feature of the C.difficile clinical strains isolated from symptomatic patients.Acquired resistance genes,alterations in the antibiotic targets and/or metabolic pathway,and biofilm formation are the main drug resistance mechanisms.Furthermore,most drug-resistant C.difficile has little fitness cost.Even in an environment lacking antibiotic selection pressure,it can still maintain drug resistance,which promotes the emergence and prevalence of multi-drug resistant strains.In recent years,the rate of C.difficile infection treatment failure with antibiotic and relapses of C.difficile infection is increasing,which pose a serious threat to public health.This article reviews recent progress of antibiotic resistance mechanisms in C.difficile,in order to offer rationales to counteract drug-resistant and develop alternative therapies.