Molecular Phylogenetics of Candida albicans

Abstract

We analyzed data on multilocus sequence typing (MLST), ABC typing, mating type-like locus (MAT) status, and antifungal susceptibility for a panel of 1,391 Candida albicans isolates. Almost all (96.7%) of the isolates could be assigned by MLST to one of 17 clades. eBURST analysis revealed 53 clonal clusters. Diploid sequence type 69 was the most common MLST strain type and the founder of the largest clonal cluster, and examples were found among isolates from all parts of the world. ABC types and geographical origins showed statistically significant variations among clades by univariate analysis of variance, but anatomical source and antifungal susceptibility data were not significantly associated. A separate analysis limited to European isolates, thereby minimizing geographical effects, showed significant differences in the proportions of isolates from blood, commensal carriage, and superficial infections among the five most populous clades. The proportion of isolates with low antifungal susceptibility was highest for MAT homozygous a/a types and then ␣/␣ types and was lowest for heterozygous a/␣ types. The tree of clades defined by MLST was not congruent with trees generated from the individual gene fragments sequenced, implying a separate evolutionary history for each fragment. Analysis of nucleic acid variation among loci and within loci supported recombination. Computational haplotype analysis showed a high frequency of recombination events, suggesting that isolates had mixed evolutionary histories resembling those of a sexually reproducing species.

Genetic and phenotypic characterization of Candida albicans strains isolated from infectious disease patients in Shanghai

“…After mechanical disruption of yeast cell walls, DNA was extracted with phenol/chloroform and precipitated with ethanol. MLST analysis and PCR amplification of the seven housekeeping genes AAT1a, ACC1, ADP1, MPIb, SYA1, VPS13 and ZWF1b were performed using the primer sequences and conditions described by Bougnoux et al (2003) and Odds et al (2007). After column purification, the PCR products were sequenced (Invitrogen) using forward and reverse primers.…”

“…The number of alleles and diploid sequence types (DSTs) was determined using the well-characterized online MLST database (http://calbicans.mlst.net/). Clades were defined and numbered as described previously (Odds et al, 2007). Isolates that did not cluster with a known clade, and clusters containing fewer than 10 isolates, were labelled as singletons.…”

Stress-Induced Phenotypic Switching inCandida albicans

“…Greater than 90% of all naturally occurring isolates of C. albicans are heterozygous at the MTL locus, containing both a and ␣ copies of the locus (Lockhart et al, 2002;Odds et al, 2007). Several natural isolates have been identified, however, that are homozygous a/a or ␣/␣ at the MTL locus and thus are competent to undergo white-opaque switching (Lockhart et al, 2002;Pujol et al, 2002;Daniels et al, 2006;Srikantha et al, 2006;Yi et al, 2008).…”

“…The white-opaque transition does not occur in MTLa/␣ cells because the a1/␣2 heterodimer inhibits WOR1 expression, thus locking cells in the white state Tsong et al, 2003;Huang et al, 2006;Srikantha et al, 2006;Zordan et al, 2006). This explains why white-opaque switching is not observed in most clinical isolates of C. albicans; only 3-8% of naturally occurring strains are homozygous at the MTL locus (Lockhart et al, 2002;Odds et al, 2007).…”

Budding off: bringing functional genomics toCandida albicans

“…population [20,21]. However, MLST karyotyping relied on genetic information at a limited number of loci, which may have obfuscated identification of hybrid strains or introgressed genomic regions resulting from sexual exchange [22].…”