Data_Sheet_5_Dissecting the Heterogeneous Population Genetic Structure of Candida albicans: Limitations and Constraints of the Multilocus Sequence Typing Scheme.PDF

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.

白色念珠菌（Candida albicans）是一种真菌机会致病菌，具有重要公共卫生意义，这主要归因于近年来致病性增强且抗真菌药物抗性菌株的不断涌现。本研究旨在通过分析白色念珠菌多位点序列分型（multilocus sequence typing, MLST）数据库Calb-MLST-DB，阐明该菌的流行病学特征并解析其种群结构；该数据库是目前已公开的该物种最大规模数据集。本研究共纳入4318条数据库分离株数据，证实了白色念珠菌的泛在分布特征：包括一组仅从健康个体中分离得到的二倍体型序列（diploid sequence types, DSTs，可作为其与宿主疾病无关联的指征）、仅从非健康个体中分离得到且可能与致病过程相关的DSTs，以及同时在健康与非健康个体中均有报道的其他DSTs。已报道的DSTs中，占比最高的样本类型为血液、口腔拭子与阴道拭子，占比分别为32.4%、20.5%和13.8%。本MLST分型方案涵盖7个持家基因（housekeeping genes），分析显示其具有较高的遗传多样性，种群结构多样，共鉴定出154个克隆复合体（clonal complexes, CCs）以及1074个单型株。对所有已报道的3483个DSTs的持家基因串联序列进行系统发育重建，其结果与CC分型仅部分一致；但由于缺乏自举置信阈值支持的分支、p距离分析无显著差异，且与其他流行病学变量无关联，反映出本MLST分型方案存在局限性。通过群体结构分析软件STRUCTURE检测到显著的遗传混合信号，结合重组检测程序RDP的分析结果，大部分混合信号可归因于重组事件，但不排除存在其他类型的基因交换事件。本研究结果进一步证实了MLST分型方案所使用基因固有的遗传多样性，这与此前提出的白色念珠菌染色体重塑现象相关，这一结论也通过微地理尺度的内部验证得到了佐证。尽管本研究结果存在偏倚——因未能纳入全球范围内广泛的白色念珠菌分离株数据——但本研究提示，应当重新评估该病原菌的种群分型策略，以优化其健康影响相关的流行病学监测工作。