Effect of N-chlorotaurine on Aspergillus, with particular reference to destruction of secreted gliotoxin.

The fungistatic and fungicidal activity of N-chlorotaurine (NCT), a long-lived oxidant produced by stimulated neutrophils, was investigated. Physiological concentrations (75-100 microM) of NCT showed clear fungicidal activity against a range of Aspergillus isolates. Moreover, killing by NCT was significantly increased in the presence of ammonium chloride, explained by the formation of monochloramine by halogenation of ammonium. One clinical isolate of Aspergillus fumigatus was characterized for the production of the immunosuppressive agent gliotoxin, and NCT was shown to cause destruction of gliotoxin, possibly via reduction of the disulphide bridge. Because of its endogenous nature and its high antifungal activity, NCT appears to be a good choice for topical treatment of Aspergillus infections, and the results of this study further substantiate its therapeutic efficacy.

Adriamycin alters the expression of drug efflux pumps and confers amphotericin B tolerance in Candida albicans.

The aim of the work presented here was to establish whether exposure of the yeast C. albicans to adriamycin altered the expression of the CDR1 drug efflux pump and consequently altered the susceptibility of the yeast to amphotericin B. Using a monoclonal antibody directed against human MDR1 and polyclonal antibodies against CDR1 (Candida drug resistance), we demonstrated that adriamycin induces an elevation in the expression of the CDR1 efflux pump which, together with previously recorded alterations in the composition of the fungal cell membrane, may confer tolerance to amphotericin B. This work highlights the fact that adriamycin therapy may inadvertently alter the susceptibility of C. albicans to amphotericin B, which may have deleterious consequences for anti-cancer chemotherapy regimes incorporating this anti-neoplastic agent.

Exposure of the yeast Candida albicans to the anti-neoplastic agent adriamycin increases the tolerance to amphotericin B.

Cancer patients experience a high incidence of fungal infections due to their immuno-suppressed condition. This work has investigated the interaction of an anti-neoplastic agent, adriamycin (doxorubicin), with the yeast Candida albicans and examined whether this drug altered the susceptibility of the yeast to amphotericin B - an anti-fungal agent used for the treatment of systemic fungal infections in cancer patients. Exposure to adriamycin for 24h increased the growth of C. albicans and increased the tolerance to amphotericin B by a small, but statistically significant, extent. Growth in adriamycin-supplemented medium suppressed the respiration rate of C. albicans, which resulted in a decrease in the ergosterol content of the fungal cell membrane. The tolerance to amphotericin B was lost after exposure to adriamycin for 48 h, which coincided with a restoration in the respiration rate and the ergosterol content of the fungal cell membrane. This work demonstrated that short-term exposure (24 h) to adriamycin increased the tolerance of C. albicans for amphotericin B, which may be mediated by a decrease in the ergosterol content as a result of an adriamycin-induced disruption of oxidative phosphorylation.