| [BACKGROUND]Candida albicans is a pathogenic yeast that causes oral, vaginal, and systemic infections, which are commonly associated with immune dysfunction, as they are frequently found in AIDS patients and transplant patients. Antifungal drugs that are available for the treatment of these infections include the polyene amphotericin B and the azoles, such as fluconazole and itraconazole. As the resistance of bacteria, that of Candida is becoming a serious challenge for our clinical doctors with the prolongation of antifungal treatment. In the past 1990s, many human immunodeficiency virus (HIV)-infected patients received long-term, low-level azole antifungal therapy, which resulted in azole-resistant isolates of C. albicans. One study documented azole resistance in up to one-third of the oral C. albicans isolates from HIV-positive patients. In recent years, resistance to antifungal drugs has been documented in other patient populations such as transplant recipients.In a clinical setting, there are many reasons why a fungal infection does not respond to antifungal drugs, including the immune status of the patient, the characteristics of the drug, and the susceptibility of the fungus to the drug. In the last several years, with the improvement of associated molecular technique and drug sensitivity test methods, some molecular mechanisms by which C. albicans develops resistance to antifungal drugs have been elucidated. The azole drugs including fluconazole target lanosterol 14 a -demethylase, the product of the ERG11 gene. Ergllp is one of the enzymes in the biosynthesis of ergosterol, the major sterol of fungal membranes and ananalogue of cholesterol in mammalian systems. Antifungal drug resistance has been associated with point mutations and increased levels of expression of the ERG11 gene. Drug efflux from the cells is another component of resistance in C. albicans, as over- expression of two types of efflux pump has been correlated with antifungal resistance. The ABC transporter genes CDRl and CDR2 encode ATP dependent efflux pumps, and the major facilitator gene MDR1 and FLU1. The overexpression of those genes is corrected with azole resistance in clinical isolates of C. albicans.[ METHODS]M27-A method based on NCCLS was used to determined the minimum inhibitory concentrations(MICs) of the clinical isolates Candida albicans from the transplant recipients, who was under immunosuppressive state.And according the results of the fluconazole sensitivity, differential expression level of CDRl mRNA was showed on the Candida albicans azole resistance and sensitive isolates, we want to discover the molecular mechanism of CDRl expression regulation by detecting whether there were the mutations on the upper stream of the CDRl gene.[RESULTS]1. Azole resistance was found in the Candida albicans isolate from the renal transplant recipients, and there is no connection between incidence of resistance and isolate locus.2. Obvious difference was showed in the expression level of CDRl gene between azole resistant and sensitive isolate.3. There is no mutation in the upper-stream regulation sequence of the CDR1 gene.[CONCLUSIONS]1. The incidence of Candida albicans azole resistance isolate from the renal transplant recipients was 36.8%(fluconazole) ~47.4%(itraconazole).2. There is cross-resistance between fluconazole and itracona-zole in the renal transplant recipients population's isolate Candida albicans.3. No connection was suggested between azole resistance and isolate locus.4. The expression level of CDR1 gene of azole resistant isolate is higher than that of azole sensitive one.5. The upper-stream regulation sequence of the CDR1 gene do not contribute to the overexpression of CDR1 gene in the Candida albicans azole resistance isolate.
|
PDF Full Text Request