Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population
Massimo Cogliati1, Alberto Zani1, Volker Rickerts2
1Lab. Micologia Medica, Dip. Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano, Italy.
Abstract:
Cryptococcus neoformans var. neoformans (serotype D) represents about 30% of the clinical isolates in Europe and is present less frequently in the other continents. It is the prevalent etiological agent in primary cutaneous cryptococcosis as well as in cryptococcal skin lesions of disseminated cryptococcosis. Very little is known about the genotypic diversity of this Cryptococcus subtype. The aim of this study was to investigate the genotypic diversity among a set of clinical and environmental C. neoformans var. neoformans isolates and to evaluate the relationship between genotypes, geographical origin and clinical manifestations. A total of 83 globally collected C. neoformans var. neoformans isolates from Italy, Germany, France, Belgium, Denmark, Greece, Turkey, Thailand, Japan, Colombia, and the USA, recovered from different sources (primary and secondary cutaneous cryptococcosis, disseminated cryptococcosis, the environment, and animals), were included in the study. All isolates were confirmed to belong to genotype VNIV by molecular typing and they were further investigated by MLST analysis. Maximum likelihood phylogenetic as well as network analysis strongly suggested the existence of a recombinant rather than a clonal population structure. Geographical origin and source of isolation were not correlated with a specific MLST genotype. The comparison with a set of outgroup C. neoformans var. grubii isolates provided clear evidence that the two varieties have different population structures.
Insights
Cryptococcus neoformans var. neoformans (serotype D) shows significant genotypic diversity, challenging a clonal population structure. Geographical origin and clinical source did not correlate with specific genotypes in this study.
Area of Science:
- Mycology
- Genetics
- Infectious Diseases
Background:
- Cryptococcus neoformans var. neoformans (serotype D) is a significant cause of cryptococcosis, particularly cutaneous forms.
- Its genotypic diversity and population structure remain poorly understood.
- This serotype is prevalent in Europe but less common globally.
Purpose of the Study:
- To investigate the genotypic diversity of clinical and environmental Cryptococcus neoformans var. neoformans isolates.
- To explore potential correlations between genotypes, geographical origin, and clinical manifestations.
- To compare the population structure of C. neoformans var. neoformans with C. neoformans var. grubii.
Main Methods:
- Molecular typing (MLST) was performed on 83 globally collected isolates.
- Phylogenetic and network analyses were used to assess population structure.
- Isolates were sourced from diverse clinical and environmental origins across multiple continents.
Main Results:
- All investigated isolates belonged to genotype VNIV.
- Multilocus sequence typing (MLST) analysis indicated a recombinant, rather than clonal, population structure.
- No significant correlation was found between MLST genotype, geographical origin, or clinical source.
- Distinct population structures were observed between C. neoformans var. neoformans and C. neoformans var. grubii.
Conclusions:
- Cryptococcus neoformans var. neoformans exhibits a recombinant population structure, not a clonal one.
- Geographical and clinical factors do not appear to drive specific MLST genotypes within this variety.
- Significant differences exist in population structure between C. neoformans var. neoformans and C. neoformans var. grubii.


