Pathogenicity and drug resistance in Candida albicans and other yeast species

Abstract

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.

Bioactivity of a Family of Chiral Nonracemic Aminobenzylnaphthols towards Candida albicans

“…In healthy individuals this colonization remains benign; however, C. albicans could pose a strong threat in immunocompromised patients, who can suffer recalcitrant infections on the skin and in the oral cavity [4]. The rise in the number of immunocompromised patients has caused a dramatic increase of the incidence of fungal infections due to C. albicans and other related human opportunistic pathogens [5,6] and this issue is a great challenge for human health due also to the fact that some strains of these yeasts are resistant to some traditional antifungals, like the azoles [7].…”

Susceptibility of Candida albicans to photodynamic therapy in a murine model of oral candidosis

“…7 Although resistance of C. albicans to polyenes is rare, several mechanisms of azole resistance 8 have been reported, including changes in the cell wall or plasma membrane, which lead to impaired azole uptake; overexpression of or mutations in the target enzyme of azoles; and the efflux of drugs mediated by membrane transport proteins. 9 Resistance appears to increase proportionally with the extend of previous exposure to the antifungal drugs. 10 Moreover, because of the fungistatic rather than fungicidal effect of azoles, 7 the host defenses are essential for eradicating the infection.…”

The anti-candidal activity of Pelargonium graveolens essential oils against clinical isolates of Candida albicans

“…The emergence of antibiotic resistant C. albicans 18,19 along with the essential role of C. albicans in high incidence of infections 20,21 have been persuaded the scientist to find the new antifungal agents especially among the medicinal plants.…”