Clonal Strain Persistence of Candida albicans Isolates from Chronic Mucocutaneous Candidiasis Patients

Abstract

Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disorder characterised by susceptibility to chronic Candida and fungal dermatophyte infections of the skin, nails and mucous membranes. Molecular epidemiology studies of CMC infection are limited in number and scope and it is not clear whether single or multiple strains inducing CMC persist stably or are exchanged and replaced. We subjected 42 C. albicans individual single colony isolates from 6 unrelated CMC patients to multilocus sequence typing (MLST). Multiple colonies were typed from swabs taken from multiple body sites across multiple time points over a 17-month period. Among isolates from each individual patient, our data show clonal and persistent diploid sequence types (DSTs) that were stable over time, identical between multiple infection sites and exhibit azole resistant phenotypes. No shared origin or common source of infection was identified among isolates from these patients. Additionally, we performed C. albicans MLST SNP genotype frequency analysis to identify signatures of past loss of heterozygosity (LOH) events among persistent and azole resistant isolates retrieved from patients with autoimmune disorders including CMC.

Fig 1. Multiple sequence alignment of concatenated SNPS of DSTs from 6 CMC patients.

Multiple sequence alignment of C. albicans MLST concatenated SNPs for the 6 DSTs. Blue and green colours are homozygous SNPs, yellow, orange, red, pink and brown are heterozygous SNPs, the boundaries of the 7 sequenced regions are indicated at the x axis. SplitsTree phylogram of the DSTs profiles appears at the y axis.

Fig 2. Normalised frequency distribution (NFD) of 6 comparator datasets.

NFD heat-map of frequency differences for six datasets (B-G) normalised against a non-redundant dataset of 2867 isolates curated at the central C. albicans database (Dataset A).