Genética da resistência ao antimicótico terbinafina

Abstract

ons in humans. Thts anthnycobc agent, « ‘^ e oup, acts by blocking the biosynthests of ergostero, ngi, by inhibiting the enzyme m«tant stratns obtained after Jtdied from genetic and physiologtcal viewp 'e b A 7 and terbAIO), whieh are h Íg W y g e n e js r e s p onsible for train F (MSF). Genetic analysts revea e a lle ,e s esistanee to terbinafine in both ' " ^ ' ’2 o i n l ) |„a l|O n u n i,s fron, the pyr„A4 ocated in chromosome IV at abou te r binafine by the diploid strains narker. Analysis o fth e levei of resistance reS ponsible for erbA7 // MSF and terbAIO / / MS m u ta n ts o f a p a r c ia l tolerance to this drug in the terbA7 a n p r a c tiCally behave as dominance or a codornínant nature pu rthermore, some mitotic dominant genes at high terbinafine con due (0 the . i hiner-resistance io u«* and meiotic segregants presen e • c e to terbinafine and the gene interaction between the gene that confe r e s e n t in chromosome II of the that confers resistance to acriflavin, d MSFshain. . a n a ly z e d showed a high Index of The resistant and sensitive st determine whether • c of the drug- . sectorization at high concentration r e v e rsal system for mehionme terbinafine has mutagenic activity, w C 1 j jc a tcd that the drug increased the ’ndependence in A. nidulans. The res spontaneous reversal. Terbinafíne also showed the ability to induce the appearance of sectors in diploid strains of this fungus. Thus, theses results suggest that terbinafíne, in addition to being an enzyme inhibitor, has a mutagenic effect on A. nidulans. Terbinafíne also proved to be able to induce the production of cleistothecia dl,ri«g the vegetative growth of this fungus. Transformation experhnents carried out in order to detennine the ex’stence of heterologous complentations of the function of resistance to terbinafíne by A. nidulans in the dermatophyte Trichophyton rubrum yielded Positive results. Preliminaiy data indicate that the transformants of T. rubrum °btained with the use of an instantaneous DNA Iibrary from an A. nidulans nutant resistant to terbinafíne showed high resistance to terbinafine compared !° dle re ceptor strain, suggesting a expression of function.