scholarly journals Genomic evidence for a hybrid origin of the yeast opportunistic pathogen Candida albicans

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Verónica Mixão ◽  
Toni Gabaldón
Keyword(s):  
Candida Albicans ◽  
Opportunistic Pathogen ◽  
Hybrid Origin

scholarly journals Genomic evidence for a hybrid origin of the yeast opportunistic pathogen Candida albicans

2019 ◽  
Author(s):  
Verónica Mixão ◽  
Toni Gabaldón
Keyword(s):  
Candida Albicans ◽  
Opportunistic Pathogen ◽  
Sexual Cycle ◽  
Hybrid Origin ◽  
Species Boundaries ◽  
Compelling Evidence ◽  
Parasexual Cycle ◽  
Evolution Of Virulence ◽  
Vertical Evolution ◽  
Current Species

AbstractOpportunistic yeast pathogens are of increasing medical concern. Candida albicans, the species with the highest incidence, is a natural commensal of humans that can adopt a pathogenic behaviour. This species is highly heterozygous, is an obligate diploid, and cannot undergo meiosis, adopting instead a parasexual cycle. The origin of these traits is unknown and we hypothesize they could result from ancestral hybridization. We tested this idea by analyzing available genomes of C. albicans isolates and comparing them to those of hybrid and non-hybrid strains of other Candida species. Our results show compelling evidence that C. albicans is an evolved hybrid, with levels and patterns of ancestral heterozygosity that cannot be fully explained under the paradigm of vertical evolution. Although the level of inferred divergence between the putative parental lineages (2.8%) is not clearly beyond current species boundaries in Saccharomycotina, we show here that all analyzed C. albicans strains derive from a single hybrid ancestor, which diverged by extensive loss of heterozygosis. This finding has important implications for our understanding of C. albicans evolution, including the loss of the sexual cycle, the origin of the association with humans, and the evolution of virulence traits.

scholarly journals Oral Administration of Lactobacillus helveticus LA401 and Lactobacillus gasseri LA806 Combination Attenuates Oesophageal and Gastrointestinal Candidiasis and Consequent Gut Inflammation in Mice

2021 ◽  
Vol 7 (1) ◽  
pp. 57
Author(s):  
Hélène Authier ◽  
Marie Salon ◽  
Mouna Rahabi ◽  
Bénédicte Bertrand ◽  
Claude Blondeau ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Oral Administration ◽  
Mannose Receptor ◽  
Opportunistic Pathogen ◽  
Protective Role ◽  
Lactobacillus Helveticus ◽  
Lectin Receptors ◽  
Lactobacillus Gasseri ◽  
Inflammatory Status ◽  
Gastrointestinal Candidiasis

Candida albicans is an opportunistic pathogen that causes mucosal gastrointestinal (GI) candidiasis tightly associated with gut inflammatory status. The emergence of drug resistance, the side effects of currently available antifungals and the high frequency of recurrent candidiasis indicate that new and improved therapeutics are needed. Probiotics have been suggested as a useful alternative for the management of candidiasis. We demonstrated that oral administration of Lactobacillus gasseri LA806 alone or combined with Lactobacillus helveticus LA401 in Candida albicans-infected mice decrease the Candida colonization of the oesophageal and GI tract, highlighting a protective role for these strains in C. albicans colonization. Interestingly, the probiotic combination significantly modulates the composition of gut microbiota towards a protective profile and consequently dampens inflammatory and oxidative status in the colon. Moreover, we showed that L. helveticus LA401 and/or L. gasseri LA806 orient macrophages towards a fungicidal phenotype characterized by a C-type lectin receptors signature composed of Dectin-1 and Mannose receptor. Our findings suggest that the use of the LA401 and LA806 combination might be a promising strategy to manage GI candidiasis and the inflammation it causes by inducing the intrinsic antifungal activities of macrophages. Thus, the probiotic combination is a good candidate for managing GI candidiasis by inducing fungicidal functions in macrophages while preserving the GI integrity by modulating the microbiota and inflammation.

scholarly journals Extreme diversification driven by parallel events of massive loss of heterozygosity in the hybrid lineage of Candida albicans

Genetics ◽  
2020 ◽  
Vol 217 (2) ◽  
Author(s):  
Verónica Mixão ◽  
Ester Saus ◽  
Teun Boekhout ◽  
Toni Gabaldón
Keyword(s):  
Candida Albicans ◽  
Loss Of Heterozygosity ◽  
Type Strain ◽  
Taxonomic Classification ◽  
Hybrid Origin ◽  
Genomic Analyses ◽  
Candida Africana

Abstract Candida albicans is the most commonly reported species causing candidiasis. The taxonomic classification of C. albicans and related lineages is controversial, with Candida africana (syn. C. albicans var. africana) and Candida stellatoidea (syn. C. albicans var. stellatoidea) being considered different species or C. albicans varieties depending on the authors. Moreover, recent genomic analyses have suggested a shared hybrid origin of C. albicans and C. africana, but the potential parental lineages remain unidentified. Although the genomes of C. albicans and C. africana have been extensively studied, the genome of C. stellatoidea has not been sequenced so far. In order to get a better understanding of the evolution of the C. albicans clade, and to assess whether C. stellatoidea could represent one of the unknown C. albicans parental lineages, we sequenced C. stellatoidea type strain (CBS 1905). This genome was compared to that of C. albicans and of the closely related lineage C. africana. Our results show that, similarly to C. africana, C. stellatoidea descends from the same hybrid ancestor as other C. albicans strains and that it has undergone a parallel massive loss of heterozygosity.

scholarly journals Investigating the Transcriptome of Candida albicans in a Dual-Species Staphylococcus aureus Biofilm Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Bryn Short ◽  
Christopher Delaney ◽  
Emily McKloud ◽  
Jason L. Brown ◽  
Ryan Kean ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Biofilm Formation ◽  
Driving Forces ◽  
Transcriptional Profiling ◽  
Specific Interaction ◽  
Opportunistic Pathogen ◽  
Virulence Proteins ◽  
Biofilm Model ◽  
Upregulated Genes

Candida albicans is an opportunistic pathogen found throughout multiple body sites and is frequently co-isolated from infections of the respiratory tract and oral cavity with Staphylococcus aureus. Herein we present the first report of the effects that S. aureus elicits on the C. albicans transcriptome. Dual-species biofilms containing S. aureus and C. albicans mutants defective in ALS3 or ECE1 were optimised and characterised, followed by transcriptional profiling of C. albicans by RNA-sequencing (RNA-seq). Altered phenotypes in C. albicans mutants revealed specific interaction profiles between fungus and bacteria. The major adhesion and virulence proteins Als3 and Ece1, respectively, were found to have substantial effects on the Candida transcriptome in early and mature biofilms. Despite this, deletion of ECE1 did not adversely affect biofilm formation or the ability of S. aureus to interact with C. albicans hyphae. Upregulated genes in dual-species biofilms corresponded to multiple gene ontology terms, including those attributed to virulence, biofilm formation and protein binding such as ACE2 and multiple heat-shock protein genes. This shows that S. aureus pushes C. albicans towards a more virulent genotype, helping us to understand the driving forces behind the increased severity of C. albicans-S. aureus infections.

scholarly journals Bifidobacterium adolescentis shows potential to strengthen host defence against gastrointestinal infection via inhibition of the opportunistic pathogen Candida albicans and stimulation of human-isolated macrophages killing capacity in vitro

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Liviana Ricci ◽  
Joanna Mackie ◽  
Megan D. Lenardon ◽  
Caitlin Jukes ◽  
Ahmed N. Hegazy ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Bacterial Species ◽  
Opportunistic Pathogen ◽  
Limited Information ◽  
Human Gut ◽  
Bifidobacterium Adolescentis ◽  
Host Immune Responses ◽  
Opportunistic Fungal Pathogen ◽  
Antimicrobial Metabolites

The human gut microbiota enhances the host’s resistance to enteric pathogens via colonisation resistance, a phenomenon that is driven by multiple mechanisms, such as production of antimicrobial metabolites and activation of host immune responses. However, there is limited information on how individual gut bacterial species, particularly many of the dominant anaerobes, might impact the host’s defence. This study investigated the potential of specific human gut isolates to bolster the host’s resistance to infection. First, by antagonising the opportunistic fungal pathogen Candida albicans, and secondly, by modulating the killing capacity of human-isolated macrophages in vitro. Co-culturing C. albicans with faecal microbiota from different healthy individuals revealed varying levels of fungal inhibition. In vitro assays with a panel of representative human gut anaerobes confirmed that culture supernatants from certain bacterial isolates, in particular of Bifidobacterium adolescentis, significantly inhibited C. albicans growth. Mechanistic studies revealed that microbial fermentation acids including acetate and lactate, in combination with the associated decrease in pH, were strong drivers of this inhibitory activity. In the second in vitro assay, human-isolated macrophages were exposed to bacterial supernatants, and subsequently tested for their capacity to eliminate adherent-invasive Escherichia coli. Among the gut anaerobes tested, B. adolescentis was revealed to exert the strongest immunostimulatory and killing effect when compared to the unstimulated macrophages control. B. adolescentis is known to be stimulated by dietary consumption of resistant starch andmay therefore represent an attractive target for the development of probiotic and prebiotic interventions tailored to enhancethe host’s natural defences against infection.

scholarly journals A Novel Function for Hog1 Stress-Activated Protein Kinase in Controlling White-Opaque Switching and Mating in Candida albicans

2014 ◽  
Vol 13 (12) ◽  
pp. 1557-1566 ◽  
Author(s):  
Shen-Huan Liang ◽  
Jen-Hua Cheng ◽  
Fu-Sheng Deng ◽  
Pei-An Tsai ◽  
Ching-Hsuan Lin
Keyword(s):  
Candida Albicans ◽  
Protein Kinase ◽  
Synthetic Medium ◽  
Opportunistic Pathogen ◽  
Phenotypic Switch ◽  
Content Type ◽  
Host Interactions ◽  
Main Pathway ◽  
Phenotypic Transition ◽  
External Stimuli

ABSTRACTCandida albicansis a commensal in heathy people but has the potential to become an opportunistic pathogen and is responsible for half of all clinical infections in immunocompromised patients. Central to understandingC. albicansbehavior is the white-opaque phenotypic switch, in which cells can undergo an epigenetic transition between the white state and the opaque state. The phenotypic switch regulates multiple properties, including biofilm formation, virulence, mating, and fungus-host interactions. Switching between the white and opaque states is associated with many external stimuli, such as oxidative stress, pH, andN-acetylglucosamine, and is directly regulated by the Wor1 transcriptional circuit. The Hog1 stress-activated protein kinase (SAPK) pathway is recognized as the main pathway for adapting to environmental stress inC. albicans. In this work, we first show that loss of theHOG1gene ina/aand α/α cells, but nota/α cells, results in 100% white-to-opaque switching when cells are grown on synthetic medium, indicating that switching is repressed by thea1/α2 heterodimer that repressesWOR1gene expression. Indeed, switching in thehog1Δ strain was dependent on the presence ofWOR1, as ahog1Δwor1Δ strain did not show switching to the opaque state. Deletion ofPBS2andSSK2also resulted inC. albicanscells switching from white to opaque with 100% efficiency, indicating that the entire Hog1 SAPK pathway is involved in regulating this unique phenotypic transition. Interestingly, all Hog1 pathway mutants also caused defects in shmoo formation and mating efficiencies. Overall, this work reveals a novel role for the Hog1 SAPK pathway in regulating white-opaque switching and sexual behavior inC. albicans.

scholarly journals Interactions between Candida albicans and Enterococcus faecalis in an Organotypic Oral Epithelial Model

2020 ◽  
Vol 8 (11) ◽  
pp. 1771
Author(s):  
Akshaya Lakshmi Krishnamoorthy ◽  
Alex A. Lemus ◽  
Adline Princy Solomon ◽  
Alex M. Valm ◽  
Prasanna Neelakantan
Keyword(s):  
Candida Albicans ◽  
Enterococcus Faecalis ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Surface Erosion ◽  
Host Immune System ◽  
Microbial Invasion ◽  
Mucosal Surfaces ◽  
Life Threatening ◽  
Hyphal Formation

Candida albicans as an opportunistic pathogen exploits the host immune system and causes a variety of life-threatening infections. The polymorphic nature of this fungus gives it tremendous advantage to breach mucosal barriers and cause oral and disseminated infections. Similar to C. albicans, Enterococcus faecalis is a major opportunistic pathogen, which is of critical concern in immunocompromised patients. There is increasing evidence that E. faecalis co-exists with C. albicans in the human body in disease samples. While the interactive profiles between these two organisms have been studied on abiotic substrates and mouse models, studies on their interactions on human oral mucosal surfaces are non-existent. Here, for the first time, we comprehensively characterized the interactive profiles between laboratory and clinical isolates of C. albicans (SC5314 and BF1) and E. faecalis (OG1RF and P52S) on an organotypic oral mucosal model. Our results demonstrated that the dual species biofilms resulted in profound surface erosion and significantly increased microbial invasion into mucosal compartments, compared to either species alone. Notably, several genes of C. albicans involved in tissue adhesion, hyphal formation, fungal invasion, and biofilm formation were significantly upregulated in the presence of E. faecalis. By contrast, E. faecalis genes involved in quorum sensing, biofilm formation, virulence, and mammalian cell invasion were downregulated. This study highlights the synergistic cross-kingdom interactions between E. faecalis and C. albicans in mucosal tissue invasion.

scholarly journals Robust, Comprehensive Molecular, and Phenotypical Characterisation of Atypical Candida albicans Clinical Isolates From Bogotá, Colombia

2020 ◽  
Vol 10 ◽  
Author(s):  
Giovanni Rodríguez-Leguizamón ◽  
Andrés Ceballos-Garzón ◽  
Carlos F. Suárez ◽  
Manuel A. Patarroyo ◽  
Claudia M. Parra-Giraldo
Keyword(s):  
Candida Albicans ◽  
Galleria Mellonella ◽  
Opportunistic Pathogen ◽  
Clinical Isolates ◽  
High Genetic Diversity ◽  
Cluster Membership ◽  
Protein Mass ◽  
Molecular Tests ◽  
Well Differentiated ◽  
Clade 1

Candida albicans is commensal in human microbiota and is known to be the commonest opportunistic pathogen, having variable clinical outcomes that can lead to up to 60% mortality. Such wide clinical behaviour can be attributed to its phenotypical plasticity and high genetic diversity. This study characterised 10 Colombian clinical isolates which had already been identified as C. albicans by molecular tests; however, previous bioinformatics analysis of protein mass spectra and phenotypical characteristics has shown that this group of isolates has atypical behaviour, sharing characteristics of both C. africana and C. albicans. This study was aimed at evaluating atypical isolates’ pathogenic capability in the Galleria mellonella model; susceptibility profiles were determined and MLST was used for molecular characterisation. Cluster analysis, enabling unbiased bootstrap to classify the isolates and establish their cluster membership and e-BURST, was used for establishing clonal complexes (CC). Both approaches involved using representative MLST data from the 18 traditional C. albicans clades, as well as C. albicans-associated and minor species. Ten atypical isolates were distributed as follows: 6/10 (B71, B41, B60, R6, R41, and R282) were grouped into a statistically well-supported atypical cluster (AC) and constituted a differentiated CC 6; 2/10 of the isolates were clearly grouped in clade 1 and were concurrent in CC 4 (B80, B44). Another 2/10 atypical isolates were grouped in clade 10 and concurred in CC 7 (R425, R111); most atypical isolates were related to geographically distant isolates and some represented new ST. Isolates B41 and R41 in the AC had greater virulence. Isolate B44 was fluconazole-resistant and was grouped in clade 1. The atypical nature of the isolates studied here was demonstrated by the contrast between phenotypical traits (C. africana-like), molecular markers (C. albicans-like), virulence, and antifungal resistance, highlighting the widely described genetic plasticity for this genus. Our results showed that the atypical isolates forming well-differentiated groups belonged to C. albicans. Our findings could contribute towards developing molecular epidemiology approaches for managing hospital-acquired infection.

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