Genetic Relationship between Cryptococcus neoformans var. neoformans Strains of Serotypes A and D

Abstract

Cryptococcus neoformans serotypes A and D are responsible for the overwhelming majority of infections in patients with AIDS. The genetic relationship between the serotypes is poorly understood, but there are significant differences in the epidemiology and clinical presentation of serotype A and D infections. We evaluated the genetic relationship between reference C. neoformansstrains belonging to serotypes A and D by analyzing theirURA5 sequences and restriction fragment length polymorphisms (RFLPs) with the C. neoformans repetitive element 1 (CNRE-1) probe. The results were compared to those previously obtained for isolates from Brazil and New York City by the same typing methods, and dendrograms were generated. Serotype A and D strains produced distinct RFLP patterns consistent with their separation into two major clusters in the dendrogram generated on the basis of RFLP data. Similarly, serotype A and D strains clustered independently on the basis of the nucleotide sequences of their URA5 genes. Pairwise comparisons revealed average 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 serotypes A and D of 41.9 ± 2.7. In summary, our results indicate phylogenetic differences between the two serotypes of C. neoformans var. neoformans and suggest that these serotypes could probably be considered different varieties of C. neoformans.

Comparative analysis of the intergenic spacer regions and population structure of the species complex of the pathogenic yeast

“…neoformans into two distinct clades has been confirmed by multiple gene analysis, i.e., IGS, ITS, laccase gene, mitochondrial large ribosomalsubunit RNA (mtLrRNA), topoisomerase (TOPI), Cap59, 26S LrRNA and URA5 gene [7,19,20,52,53]. Some of these studies have reported the presence of considerable sequence divergence between these varieties, namely up to 6% for the URA5 gene [7], 3.6% for the topoisomerase I gene [1] and 8% for a partial analysis of the IGSI region [19]. When both intergenic spacers (IGSII + 5S rRNA + IGSII) were combined, the sequence divergence increased to nearly 12%.…”

“…However, more samples need to be analyzed to elucidate the allelic structure of serotype-AD isolates at the IGS locus. Although serotype-AD strains are known to be diploids [17,49,51,58,59,61,62], there are many AD isolates reported as haploids [62][63][64][65] and aneuploids [7]. For example, the existence of a single STE20 allele and one mating-type allele has been reported to occur in serotype-AD strains [63,64].…”

“…neoformans and Cryptococcus gattii have been reported as ethiological agents of cryptococcosis in HIV-infected patients [5][6][7][8]. C. neoformans var.…”

Cryptococcosis: update and emergence ofCryptococcus gattii

“…grubii , and C. gattii . Interspecies hybrids of C. neoformans and C. gattii may occur both in vitro and in vivo, and distinction of these organisms as 2 separate species has been recently confirmed by molecular techniques and genomic analysis 6–8 . Their classification was originally based on serotype as determined by their capsular antigens, and they were divided as C. neoformans var.…”

“…neoformans serotype D, C. neoformans var. grubii serotype A, with an additional mixed serotype AD (diploid hybrid), and C. gattii serotype B or C 4,7 . Genotyping has now replaced serologic typing for the classification of these organisms, as the molecular genotype is more precise and aids in understanding relationships both within and between geographic areas.…”