Canavanine resistance in Cryptococcus neoformans.

All of the isolates of Cryptococcus neoformans var. gattii which we tested were resistant to greater than or equal to 3.5 mM canavanine. All of the serotype D isolates and 28% of the serotype A isolates of C. neoformans var. neoformans tested were susceptible to less than or equal to 18 microM canavanine, whereas the remaining 72% of the serotype A isolates were as resistant as the C. neoformans gattii isolates. In the naturally resistant isolates, the mechanism of resistance appeared to be decomposition of canavanine to a nontoxic product. However, in a resistant mutant derived from a naturally susceptible isolate, the mechanism of resistance was an impaired uptake system for canavanine. The toxic effect of canavanine in Cryptococcus results from the incorporation of canavanine into the protein component that is essential for the synthesis of proteins and RNAs.