GENETIC-RELATIONSHIP BETWEEN CRYPTOCOCCUS-NEOFORMANS VAR. NEOFORMANS STRAINS OF SEROTYPE-A AND SEROTYPE-D

Cryptococcus neoformans serotypes A and D are responsible for the over whelming majority of infections in patients with AIDS. The genetic rel ationship between the serotypes is poorly understood, but there are si gnificant differences in the epidemiology and clinical presentation of serotype A and D infections. We evaluated the genetic relationship be tween reference C. neoformans strains belonging to serotypes A and D b y analyzing their URA5 sequences and restriction fragment length polym orphisms (RFLPs) with the C. neoformans repetitive element 1 (CNRE-1) probe. The results were compared to those previously obtained for isol ates from Brazil and New York City by the same typing methods, and den drograms were generated. Serotype A and D strains produced distinct RF LP patterns consistent with their separation into two major clusters i n the dendrogram generated on the basis of RFLP data. Similarly, serot ype A and D strains clustered independently on the basis of the nucleo tide sequences of their URA5 genes. Pairwise comparisons revealed aver age numbers of nucleotide differences within serotypes A and D of 3.0 +/- 1.7 and 7.2 +/- 3.4, respectively (P < 0.0001), and between seroty pes A and D of 41.9 +/- 2.7. In summary, our results indicate phylogen etic differences between the two serotypes of C. neoformans var, neofo rmans and suggest that these serotypes could probably be considered di fferent varieties of C. neoformans.