Investigation of Candida parapsilosis virulence regulatory factors during host-pathogen interaction

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• dc.contributor.author Tóth, Renáta
• dc.contributor.author Cabral, Vitor
• dc.contributor.author Thuer, Ernst, 1986-
• dc.contributor.author Bohner, Flóra
• dc.contributor.author Németh, Tibor
• dc.contributor.author Papp, Csaba
• dc.contributor.author Nimrichter, Leonardo
• dc.contributor.author Molnár, Gergő
• dc.contributor.author Vágvölgyi, Csaba
• dc.contributor.author Gabaldón Estevan, Juan Antonio, 1973-
• dc.contributor.author Nosanchuk, Joshua D.
• dc.contributor.author Gácser, Attila
• dc.date.accessioned 2019-12-09T09:23:18Z
• dc.date.available 2019-12-09T09:23:18Z
• dc.date.issued 2018
• dc.description.abstract Invasive candidiasis is among the most life-threatening infections in patients in intensive care units. Although Candida albicans is the leading cause of candidaemia, the incidence of Candida parapsilosis infections is also rising, particularly among the neonates. Due to differences in their biology, these species employ different antifungal resistance and virulence mechanisms and also induce dissimilar immune responses. Previously, it has been suggested that core virulence effecting transcription regulators could be attractive ligands for future antifungal drugs. Although the virulence regulatory mechanisms of C. albicans are well studied, less is known about similar mechanisms in C. parapsilosis. In order to search for potential targets for future antifungal drugs against this species, we analyzed the fungal transcriptome during host-pathogen interaction using an in vitro infection model. Selected genes with high expression levels were further examined through their respective null mutant strains, under conditions that mimic the host environment or influence pathogenicity. As a result, we identified several mutants with relevant pathogenicity affecting phenotypes. During the study we highlight three potentially tractable signaling regulators that influence C. parapsilosis pathogenicity in distinct mechanisms. During infection, CPAR2_100540 is responsible for nutrient acquisition, CPAR2_200390 for cell wall assembly and morphology switching and CPAR2_303700 for fungal viability.
• dc.description.sponsorship The project was subsidized by the European Union and co-financed by the European Social Fund. AG was funded by NKFIH NN 113153, by GINOP-2.3.2-15-2016-00035, by GINOP-2.3.3-15-2016-00006. AG and LN were also founded by CNPq (Program Science without borders - 407380/2013-2). TN was supported by the Postdoctoral Fellowship by the Hungarian Academy of Sciences. Research at TG lab was partially funded by grants from Spanish Ministry of Economy and Competitiveness BFU2015-67107 cofounded by European Regional Development Fund (ERDF); from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreements FP7-PEOPLE-2013-ITN-606786 “ImResFun” and from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No H2020-MSCA-ITN-2014-642095. JDN is partially supported by US NIH grants R21 AI124797-02 and AI52733-06A2. We would like to thank Prof. Geraldine Butler for the KO strategy and parental strains necessary for mutant strain generation. We would like to thank Chetna Tyagi for the help with the in silico data analyses, Mónika Homolya for contributing to the chitinase and chitin synthase expression experiments, Dr. Sándor Kocsubé for the summary table and Tamás Petkovits for the help with the SEM experiments.
• dc.format.mimetype application/pdf
• dc.identifier.citation Tóth R, Cabral V, Thuer E, Bohner F, Németh T, Papp C et al. Investigation of Candida parapsilosis virulence regulatory factors during host-pathogen interaction. Sci Rep. 2018;8(1):1346. DOI: 10.1038/s41598-018-19453-4
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-018-19453-4
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/43122
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Scientific Reports. 2018;8(1):1346
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-67107
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/606786
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/642095
• dc.rights © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Fungal immune evasion
• dc.subject.keyword Fungal pathogenesis
• dc.title Investigation of Candida parapsilosis virulence regulatory factors during host-pathogen interaction
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion