Abstract
Members of the Cryptococcus complex, includes Cryptococcus neoformans (most common fungal infection of the brain) and Cryptococcus gattii (high-impact emerging pathogen worldwide). Currently, the fungal multilocus sequence typing database (Fungal MLST Database) constitutes a valuable data repository of the genes used for molecular typing of these pathogens. We analyzed the data available in the Fungal MLST Database for seven housekeeping genes, with the aim to evaluate its contribution in the description of intra-taxa diversity, population genetic structure, and evolutionary patterns. Although the Fungal MLST Database has a greater number of reports for C. neoformans (n = 487) than for C. gattii (n = 344), similar results were obtained for both species in terms of allelic diversity. Phylogenetic reconstructions revealed grouping by molecular type in both species and allowed us to propose differences in evolutionary patterns (gradualism in the case of C. neoformans and punctuated evolution in the case of C. gattii). In addition, C. neoformans showed a population genetic structure consisting of 37 clonal complexes (CCs; CC1 being predominant), high crosslinking [without sequence type (ST) grouping by molecular type], marked divergence events in phylogenetic analysis, and few introgression events (mainly between VNI and VNIV). By contrast, C. gattii showed 50 CCs (with greater homogeneity in ST number by CC) and clustering by molecular type with marked crosslinking events in phylogenetic networks being less evident. Understanding relationships at the molecular level for species of the Cryptococcus complex, based on the sequences of the housekeeping genes, provides information for describing the evolutionary history of these emerging pathogens.
Highlights
The public health importance of the Cryptococcus complex has been confirmed by epidemiological data, indicating more than 620,000 deaths annually (Springer et al, 2014)
A total of 849 sequence type (ST) of the Cryptococcus complex were identified in the Fungal multilocus sequence typing (MLST) Database on the last access date, corresponding to 487 STs for C. neoformans, higher than those found for C. gattii (362 STs)
As for the number of alleles identified for MLST genes used in the scheme, we found that C. gattii possessed more alleles for all of the genes, except for URA5 where the number of alleles was similar between the two species
Summary
The public health importance of the Cryptococcus complex has been confirmed by epidemiological data, indicating more than 620,000 deaths annually (Springer et al, 2014). C. neoformans is recognized as the most widely distributed species worldwide, mainly infecting immunocompromised individuals (Barreto de Oliveira et al, 2004; Idnurm et al, 2005) This pathogen has been the focus of many studies aimed at identifying the mechanisms related to pathogenesis, with the goal of identifying potential therapeutic targets (Lin, 2009; Ding et al, 2016; Taylor-Smith and May, 2016). Regarded as being restricted to tropical and subtropical regions, this pathogen was subsequently found to be associated with outbreaks in temperate regions, involving infections not associated with immunosuppression (Stephen et al, 2002; Datta et al, 2009; Ngamskulrungroj et al, 2011) These reports have focused attention on the virulence of C. gattii as a primary and emerging pathogen, with wide geographical distribution and an annual increase in the number of cases (Kidd et al, 2004; Byrnes et al, 2010, 2011)
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