Resistance to fluconazole by efflux ans its pharmacological reversion [Resistência ao fluconazol por efluxo e sua reversão farmacológica]

• Type: Article in International Scientific Journal
• Date: 2002

Authors

pina-vaz, c (Author) FMUP; gonçalves rodrigues, a (Author) FMUP; costa-de-oliveira, s (Author) FMUP; tavares, c (Author) Other

Journal

Title: Arquivos de Medicina

Vol. 16

Pages: 219-225

ISSN: 0871-3413

Publisher: A E F M U P, Alameda prof. H. Montiero

Indexing

ISI Web of Knowledge

Scopus - 0 Citations

Other information

Authenticus ID: P-007-AAA

Abstract (EN): Summary: Multidrug resistance in pathogenic yeasts has been related to efflux pumps that export the drugs, therefore reducing their toxicity. Some compounds (modulators) have the capacity to block these proteins. We tested 4 drugs as potential modulators of resistance on Candida spp to fluconazole (Flu): verapamil, ß-estradiol and progesterone, three known inhibitors of efflux pumps on human neoplastic cells and ibuprofen. Ibuprofen has a documented fungicidal activity at high concentrations but shows at lower doses a synergistic effect with Flu mainly on resistant strains, unrelated with the fungicidal mechanism. As it is a lipophilic compound, like other modulators, we decided to study its capacity to revert resistance by blockade of efflux pumps. Ten clinical isolates of Candida resistant to Flu and 2 sensitive were incubated with sub-inhibitory concentrations of verapamil (100 ¿M), ß-estradiol (50 ¿M), progesterone (50 ¿M) or ibuprofen (500 ¿M/ml). MIC values to Flu associated to each modulator were determined. Yeast cells exposed and not exposed to the modulators were stained with FUN-1 (a fluorescent probe) and analyzed by FC. MIC values decreased whenever Flu was associated with the different modulators in most strains. Only C. krusei and sensitive strains did not show significant MIC variation. The FC results showed that on strains where MIC values to Flu were reduced by the modulators FUN-1 staining increased, except for C. glabrata. Most of the resistant strains tested seem to have efflux pumps that are blocked by the compounds used, reverting the resistant phenotype. FUN-1 is a useful probe that can be used to detect efflux pumps. On C. glabrata the modulators blocked the transport of Flu but not of FUN-1. The hormones and specially ibuprofen, associated with Flu, migth be promising in the clinical management of candidosis.

Language: Portuguese

Type (Professor's evaluation): Scientific

No. of pages: 7