Population Analysis of Candida dubliniensis Using Multilocus Sequence Typing (MLST)

Objectives: To investigate the usefulness of MLST for investigating the population structure of the human opportunistic yeast pathogen C. dubliniensis relative to previously used methods, including Cd25-DNA fingerprinting and ribosomal gene internal transcribed spacer (ITS) region sequencing. Human C. dubliniensis isolates recovered from disparate geographic locations around the world and isolates from seabirds were examined. A common MLST scheme was applied to C. dubliniensis and its closest relative C. albicans in order to compare their respective population structures. Methods: DNA sequence analysis of 10 loci previously tested for C. albicans MLST was undertaken with 50 epidemiologically unrelated human C. dubliniensis isolates recovered in 18 different countries, and six ITS-genotype 1 isolates recovered from seabirds. Representative isolates were included from three previously identified Cd25-defined clades and four ITS-genotypes. Fifty C. albicans isolates representative of 17 previously defined MLST clades were also included in the study. Sequences were concatenated and used in the construction of a C. dubliniensis UPGMA dendrogram and a maximum parsimony tree that enabled comparative population structures analysis of the two Candida species. Results: An UPGMA dendrogram generated from concatenated sequences revealed that the population of C. dubliniensis consists of three closely related clades, termed C1-C3, respectively. The avian C. dubliniensis isolates clustered with all of the human ITS-genotype 1 isolates tested in clade C1, the most closely related MLST clade. However, the avian isolates were dispersed throughout this clade. Maximum parsimony trees based on MLST data from all C. dubliniensis and C. albicans isolates revealed significantly less divergence within C. dubliniensis compared to C. albicans. Conclusion: The study revealed that the population structure of C. dubliniensis is significantly less divergent than that of C. albicans. The close relationship between human and avian C. dubliniensis isolates suggests possible transmission between these two hosts.