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.

Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen

“…These events involved very long LOH tracts (0.27–1.23 Mb) that extended to the ends of the chromosomes. Previous studies also detected large LOH events in C. albicans strains grown both in vitro and in vivo ( 21 , 22 , 24 , 25 , 71 , 93 ). We note that while large-scale chromosomal changes are relatively rare, these impact numerous genes and are therefore the most likely to have phenotypic consequences.…”

Multilocus sequence typing of Candida albicans isolates from the oral cavities of patients undergoing haemodialysis

“…It is generally thought that individuals are colonised by a single C. albicans strain or by several very similar strains 46 . Strains may persist over time and the same strain type can be present at multiple body sites in the same patient 44 , 46 – 54 . Therefore, we restricted the MLST analysis to only one isolate per individual.…”

“…Several studies of geographically close populations indicate that C. albicans STs concentrate within certain clades that reflect not only the geographical location but also the host’s physical status. For example, C. albicans isolates obtained from blood cultures from healthy individuals in Scotland 56 , the oral cavities of students from throughout the UK 57 , and the oral cavities of chronic mucocutaneous candidiasis patients throughout the UK 54 were mainly grouped into Clades 1, 2, and 4 (not necessarily in that order of abundance). However, C. albicans isolates from intensive care unit patients in Leeds, England, were concentrated in Clades 2, 1, and 3 46 .…”

Population structure and molecular genetic characterization of clinical Candida tropicalis isolates from a tertiary-care hospital in Kuwait reveal infections with unique strains

“…This is in contrast to C . albicans where sequential/multiple clinical isolates from various anatomical sites of the same patient have been shown by MLST analyses to be genetically identical or highly similar [ 56 , 58 – 62 ].…”