Pathogenicity and drug resistance in Candida albicans and other yeast species. A review.
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 Erg11p (lanosterol 14alpha-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.
Mishra
Nagendra Nath
NN
Department of Biotechnology, Seth J. M. Institute of Engineering and Technology, Radaur-135133, Yamuna Nagar, India. nagendranathmishra@yahoo.co.in
Prasad
Tulika
T
Sharma
Neeraj
N
Payasi
Anurag
A
Prasad
Rajendra
R
Gupta
Dwijendra K
DK
Singh
Randhir
R
D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002175:Candida / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D025141:Drug Resistance, Fungal / Q000235:genetics; D006801:Humans; D015003:Yeasts
D000935:Antifungal Agents; D001393:Azoles