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Comparative transcriptomic analysis of the response of CUG-clade Candida species to phagocytosis

ABSTRACT: Pathogenic Candida fungi are a leading cause of opportunistic, hospital-associated bloodstream infections with high mortality rates, typically in immunocompromised patients. Several species, including C. albicans, the most prevalent cause of infection, belong to the monophyletic CUG clade of yeasts. Much is known about the interaction of C. albicans with innate immune cells, which are crucial for controlling infection. Phagocytosis of C. albicans elicits transcriptional induction of several pathways involved in catabolism of non-glucose carbon sources that are important for virulence, termed alternative carbon metabolism. However, the response of other CUG clade species has not been characterized. Here, we analyzed the transcriptional responses to macrophage phagocytosis by seven Candida species across a range of virulence and clinical importance. We observed a strikingly high degree of conservation even in species that rarely cause infection and defined a core induced response linked to alternative carbon metabolism. Many of these genes showed convergence to the same level of expression upon phagocytosis. Some differences were observed, however, including notably deficient expression of heat shock protein HSP21 in common pathogen C. parapsilosis that may be linked to reduced thermotolerance in this species. In contrast, C. parapsilosis showed a more robust induction of metabolite transporters compared to the related L. elongisporus, which rarely causes infection. This study significantly broadens our understanding of host interactions in CUG clade species and shows that while metabolic plasticity is an important attribute in pathogenic Candida species, it is neither an adaptation to, nor sufficient for, virulence.

ORGANISM(S): Mus musculus Clavispora lusitaniae Candida dubliniensis Candida albicans Candida tropicalis Lodderomyces elongisporus Candida parapsilosis

PROVIDER: GSE151288 | GEO | 2021/11/28

REPOSITORIES: GEO

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Project description:Abstract: Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CUG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of >200 C. parapsilosis strains carrying double allele deletions of transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in > 40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance. Others are unique. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis and not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified 7 transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1, and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. In addition, two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic. C. parapsilosis mRNA profiles of wild type (WT) at 37 degree celcius in planktonic growth conditions and ace2-/-, cph2-/-, efg1-/-, czf1-/-, ume6-/-, bcr1-/- and WT in biofilm conditions were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.

Project description:This is genome-scale metabolic model of Candida albicans as the representative yeast species for the clade CUG-Ser1. This model was generated through homology search using a fungal pan-GEM largely based on Yeast8 for Saccharomyces cerevisiae, in addition to manual curation. This model has been produced by the Yeast-Species-GEMs project from Sysbio (www.sysbio.se). This is model version 1.0.0 accompanying the publication (DOI: 10.15252/msb.202110427), currently hosted on BioModels Database and identified by MODEL2109130014. Further curations of this model will be tracked in the GitHub repository: https://github.com/SysBioChalmers/Yeast-Species-GEMs Models for species of the same clade includes: Babjeviella inositovora; Candida albicans; Candida auris; Candida carpophila; Candida dubliniensis; Hyphopichia homilentoma; Candida intermedia; Candida orthopsilosis; Candida parapsilosis; Candida sojae; Suhomyces tanzawaensis; Yamadazyma tenuis; Candida tropicalis; Clavispora lusitaniae; Debaryomyces hansenii; Hyphopichia burtonii; Lodderomyces elongisporus; Metschnikowia aberdeeniae; Metschnikowia arizonensis; Metschnikowia bicuspidata var. bicuspidata; Metschnikowia borealis; Metschnikowia bowlesiae; Metschnikowia cerradonensis; Metschnikowia continentalis; Metschnikowia dekortorum; Metschnikowia drakensbergensis; Metschnikowia hamakuensis; Metschnikowia hawaiiensis; Metschnikowia hibisci; Metschnikowia ipomoeae; Metschnikowia kamakouana; Metschnikowia kipukae; Metschnikowia lochheadii; Metschnikowia matae var. matae; Metschnikowia matae var. maris; Metschnikowia mauinuiana; Metschnikowia proteae; Metschnikowia santaceciliae; Metschnikowia shivogae; Metschnikowia similis; Meyerozyma guilliermondii; Millerozyma acaciae; Priceomyces haplophilus; Scheffersomyces lignosus; Scheffersomyces stipitis; Spathaspora arborariae; Spathaspora girioi; Spathaspora gorwiae; Spathaspora hagerdaliae; Spathaspora passalidarum; Wickerhamia fluorescens; Priceomyces medius; Candida athensensis; Candida schatavii; Candida restingae; Aciculoconidium aculeatum; Kodamaea laetipori; Danielozyma ontarioensis; Candida oregonensis; Candida fructus; Candida corydali; Cephaloascus albidus; Cephaloascus fragrans; Suhomyces pyralidae; Suhomyces canberraensis; Suhomyces emberorum; Teunomyces kruisii; Teunomyces gatunensis; Teunomyces cretensis; Yamadazyma nakazawae; Priceomyces carsonii; Priceomyces castillae; Candida fragi; Hyphopichia heimii; Candida blattae; Yamadazyma philogaea; Yamadazyma scolyti; Meyerozyma caribbica; Kurtzmaniella cleridarum; Kodamaea ohmeri; Candida rhagii; Candida gotoi; Candida heveicola; Debaryomyces prosopidis; Debaryomyces nepalensis; Debaryomyces maramus; Candida hawaiiana; Debaryomyces subglobosus; Debaryomyces fabryi; Candida tammaniensis; Candida wancherniae; Candida ascalaphidarum; Candida golubevii; Candida gorgasii. These models are available in the zip file. To cite BioModels, please use: V Chelliah et al; BioModels: ten-year anniversary. Nucleic Acids Res 2015; 43 (D1): D542-D548. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to MIT License for more information.

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Comparative transcriptomic analysis of the response of CUG-clade Candida species to phagocytosis

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