Growth response of several Candida albicans strains to inhibitory concentrations of heavy metals

Prolonged exposure of several Candida albicans strains to inhibitory concentrations of Cd, Cu, or Zn resulted in the appearance of resistant colonies at frequencies and with kinetics significantly different than expected based solely upon the predicted spontaneous mutation rate. Characteristics of the response included: (i) a delay usually of 4-10 days in the emergence of the first resistant colonies; (ii) continued accumulation of resistant colonies for a minimum of 21 days after initial exposure to selection; and (iii) final mutation frequencies ranging from 7.0 x 10(-6) to 9.8 x 10(-4). Further examination of the response of one of the strains to Cd, demonstrated that pretreatment with either ultraviolet irradiation or hydroxyurea resulted in approximately a 10-fold increase in the number of resistant colonies detected. While the distribution and identity of colony phenotypes was altered for all strains after exposure to the heavy metals, no specific morphologies could be correlated to development of resistance.