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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.

SUBMITTER: Moorhouse AJ

PROVIDER: S-EPMC4743940 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Oropharyngeal candidiasis (OPC) is the most prevalent oral infection in immunocompromised patients, primarily associated with Candida albicans. Increasing evidence points to a significant role of mucosal bacteria on the transition of C. albicans from commensal to pathogenic. In this work, we hypothesized that changes in the abundance or composition of the mucosal bacterial microbiota induced by dietary sucrose during the development of OPC can modulate C. albicans virulence. C. albicans burdens and mucosal lesions were evaluated in a mouse cortisone immunosuppression model amended with sucrose. We also analyzed the mucosal bacterial composition using 16S rRNA gene sequencing and culture methods. In immunocompetent mice, sucrose significantly increased total bacterial burdens and reduced alpha diversity, by increasing the relative abundance of mitis group streptococci. In immunocompromised mice, C. albicans infection was associated with a significantly reduced bacterial alpha diversity due to an increase in the relative abundance of enterococci. When exposed to dietary sucrose, these mice had reduced C. albicans burdens and reduced bacterial alpha diversity, associated with an increase in the relative abundance of Lactobacillus. SparCC correlation networks showed a significant negative correlation between Lactobacillus and Enterococcus in all Candida-infected mice. Depletion of lactobacilli with antibiotic treatment partially restored C. albicans burdens in mice receiving sucrose. In coculture in vitro experiments, mouse oral Lactobacillus johnsonii isolates inhibited growth of Enterococcus faecalis isolates and C. albicans. These results support the hypothesis that the sucrose-induced attenuation of C. albicans virulence was a result of changes in the mucosal bacterial microbiome characterized by a reduction in enterococci and an increase in lactobacilli. IMPORTANCE By comparing Candida albicans virulence and the mucosal bacterial composition in a mouse oral infection model, we were able to dissect the effects of the host environment (immunosuppression), infection with C. albicans, and local modulating factors (availability of sucrose as a carbon source) on the mucosal bacterial microbiome and its role on fungal virulence. We showed that changes in endogenous microbial communities in response to sucrose can lead to attenuation of fungal disease. We also showed that Lactobacillus johnsonii may curtail Candida virulence both by inhibiting its growth and by inhibiting the growth of potentially synergistic bacteria such as enterococci. Our results support the concept that Candida pathogenesis should be viewed in the contexts of both a susceptible host and a mucosal bacterial microbiota conducive to virulence.

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

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