Abstract
Candida albicans is a fungal opportunistic pathogen of significant public health importance mainly due to the recent emergence of strains with increased aggressiveness and antifungal resistance. Here, we aimed to describe the epidemiological profiles and approximate the population structure of C. albicans by analyzing the C. albicans multilocus sequence typing (MLST) database (Calb-MLST-DB), which contains the largest publically available dataset for this species. Based on 4,318 database isolates, we confirmed the ubiquitous nature of C. albicans including a group of diploid sequence types (DSTs) obtained from Healthy individuals exclusively (taken as an indicator of lack of association with illnesses in its host), until isolates established from Non-Healthy individuals (potentially associated with pathogenic processes) and other DSTs reported in both types (Healthy and Non-Healthy). The highest number of reported DSTs was related to blood, oral and vaginal swabs (32.4, 20.5, and 13.8%, respectively). High genetic diversity was observed in the seven housekeeping genes included in the MLST scheme, with a diverse population structure (154 clonal complexes, CCs; and a high number of singletons, n = 1,074). Phylogenetic reconstruction on the concatenated alignment of these housekeeping genes for all the reported DSTs (n = 3,483) was partially concordant with the CC assignment, however, an absence of bootstrap threshold supported nodes or p-distance, and the lack of association with the other epidemiological variables, evidenced the limitations of the MLST scheme. Marked genetic admixture signals were identified by STRUCTURE, with the majority being attributable to recombination events according to the RDP program results, although another type of exchange event cannot be ruled out. Our results reaffirm the genetic diversity inherent in the genes used for the MLST scheme, which are associated with the chromosomal remodeling already proposed for C. albicans. This was also corroborated with an internal validation at a micro geographical scale. Despite these results are biased due to the unavailability of considering the broad global spectrum of C. albicans isolates around the world. This suggests that the strategy used to population type this pathogen should be reevaluated to improve epidemiological monitoring of its health impact.
Highlights
Candida albicans, a ubiquitous eukaryotic yeast, can colonize humans, other animals and a wide range of ecological niches (Hall and Noverr, 2017)
The Multilocus sequence typing (MLST) scheme for C. albicans that was proposed in 2003 (Bougnoux et al, 2003) has made it possible to advance in the characterization of populations of this fungal pathogen (McManus and Coleman, 2014) and make preliminary proposals about its population structure at the genetic level (McManus and Coleman, 2014), no molecular epidemiology analysis of the isolates by this type of analysis has been done at a global scale
This study aimed to describe the epidemiological profiles, analyze the molecular characteristics, and make an approximation of the population structure of a set of C. albicans isolates typed using the C. albicans MLST scheme globally approved (Bougnoux et al, 2003, 2004) and submitted to PubMLST databases (Jolley and Maiden, 2010)
Summary
A ubiquitous eukaryotic yeast, can colonize humans, other animals and a wide range of ecological niches (Hall and Noverr, 2017). The proliferation of C. albicans is associated with a wide spectrum of diseases (from urogenital to deep-seated infections, mainly in hospitalized patients), which cause high morbidity and mortality, making it the most common opportunistic fungal pathogen of public health importance over the last two decades (Poulain, 2015). The study of the genetic diversity in Candida species has allowed researchers to identify associations with severe infections, and for that reason, different typing methods have been employed to describe the epidemiological profiles for those species (Garcia-Hermoso et al, 2016). Multilocus sequence typing (MLST) was proposed as a high-resolution method based on nucleotide polymorphisms in multiple housekeeping genes, which allow the identification of the unique diploid sequence types (DSTs) (Tomasini et al, 2014), that can be even used in medically important fungal species (Alanio et al, 2017). A consensus MLST scheme for C. albicans, based on the following housekeeping genes, was selected: aspartate aminotransferase (AAT1a), acetyl-CoA carboxylase (ACC1), ATP-dependent permease (ADP1), mannose phosphate isomerase (MPIb), alanyl-RNA synthetase (SYA1), vacuolar protein sorting (VPS13), and glucose-6-phosphate dehydrogenase (ZWF1b) (Bougnoux et al, 2003, 2004)
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