Pathogenicity and drug resistance in Candida albicans and other yeast species
Pathogenicity and drug resistance in Candida albicans and other yeast species
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DOI：
10.1556/amicr.54.2007.3.1
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发表时间：
2007-09-01
影响因子：
1.5
通讯作者：
Singh, Randhir
中科院分区：
文献类型：
--
作者：
Mishra, Nagendra Nath;Prasad, Tulika;Singh, Randhir
来自念珠菌属的致病性酵母可在人类中引起严重感染，特别是在免疫功能低下的患者中，并且现在被认为是医院获得性（医院内）感染的主要病原体。近年来，念珠菌病患者长期接受抗真菌治疗失败的发生率显著增加，这给其在化疗中的成功使用带来了严重问题。念珠菌细胞在治疗过程中获得耐药性（MDR）。念珠菌对唑类抗真菌剂的耐药机制已被阐明，主要可分为：（i）细胞壁或质膜的变化，导致药物（唑类）摄取受损;（ii）药物靶标Erg 11 p的亲和力的改变（羊毛甾醇14 α-脱甲基酶），特别是唑类或由于ERG 11基因的靶位点突变或过表达而在Erg 11 p的细胞内容物中;和（iii）由膜转运蛋白介导的药物外排，所述膜转运蛋白属于ATP结合盒（ABC）转运蛋白，即CDR 1和CDR 2，或属于主要易化剂超家族（MFS）转运蛋白CaMDR 1。许多这样的表现与念珠菌生物膜的形成有关，包括发生在诸如留置血管内导管的装置上的那些。生物被膜相关念珠菌对广谱抗真菌药物表现出一致的耐药性。不同耐药机制的组合是念珠菌属临床分离株耐药性的原因。
Pathogenic yeasts from the genus Candida can cause serious infection in humans particularly, in immunocompromised patients and are now recognized as major agents of hospital acquired (nosocomial) infections. In the recent years, there has been a marked increase in the incidence of treatment failures in candidiasis patients receiving long-term antifungal therapy, which has posed a serious problem in its successful use in chemotherapy. Candida cells acquire drug resistance (MDR) during the course of the treatment. The mechanisms of resistance to azole antifungal agents have been elucidated in Candida species and can be mainly categorized as (i) changes in the cell wall or plasma membrane, which lead to impaired drug (azole) uptake; (ii) alterations in the affinity of the drug target Erg 11 p (lanosterol 14 alpha-demethylase) especially to azoles or in the cellular content of Erg11p due to target site mutation or overexpression of the ERG11 gene; and (iii) the efflux of drugs mediated by membrane transport proteins, belonging to the ATP-binding cassette (ABC) transporters, namely CDR1 and CDR2 or to the major facilitator superfamily (MFS) transporter, CaMDR1. Many such manifestations are associated with the formation of Candida biofilms including those occurring on devices like indwelling intravascular catheters. Biofilm-associated Candida show uniform resistance to a wide spectrum of antifungal drugs. A combination of different resistance mechanisms is responsible for drug resistance in clinical isolates of Candida species.