Relative susceptibilities of caffeine-sensitive and caffeine-resistant strains of Candida albicans to inactivation and mutation by ultraviolet radiation.

Abstract

Stable variants having increased resistance to growth inhibition by caffeine were obtained from four different absolute, amino acid auxotrophs of Candida albicans. Differences in growth rates and expression of auxotrophy between the resistant (CafR) variants and their sensitive (CafS) progenitors suggest that caffeine resistance arises through suppressor mutations which affect the fidelity of messenger RNA translation. Both CafS and CafR strains of C. albicans are more susceptible to inactivation by ultraviolet radiation (uv) when grown at 37°C rather than 25°C following exposure. Post irradiation growth on caffeine potentiates ultraviolet inactivation of all CafS strains at both temperatures. Depending on its origin, a CafR strain (i) may show greater, lesser or the same intrinsic susceptibility to uv inactivation as its CafS parent at 25°C or at 37°C and (ii) may or may not be refractory to post-irradiation contact with caffeine. CafR variants independently isolated from a given auxotroph are alike in inactivational responses whereas those obtained from different auxotrophs are dissimilar. This implies that different suppressor mutations are unique in the way they affect expression of potentially lethal uv damage and that only one kind of suppressor is obtained by selection for caffeine resistance in a particular auxotroph. The histidine requiring CafR strain WB-2CR is much more resistant to uv inactivation that its CafS parent WB-2. Moreover, post-irradiation survival of WB-2CR is unaffected by caffeine. However, WB-2CR and WB-2 are equally susceptible to uv-induced reversion to prototrophy. In both strains, caffeine does not enhance uv-induced reversion at 25°C or 37°C and exhibits an antimutagenic activity at high uv dosage at 37°C. The findings reinforce previously reported indications that, in C. albicans, (i) caffeine-sensitive excision-repair of uv damaged DNA does not occur and (ii) caffeine potentiates uv cellular inactivation by disturbing post-irradiation synthesis of protein essential for recovery from non-genetic damage.