TY - JOUR
T1 - Investigation of Candida parapsilosis virulence regulatory factors during host-pathogen interaction
AU - Tóth, Renáta
AU - Cabral, Vitor
AU - Thuer, Ernst
AU - Bohner, Flóra
AU - Németh, Tibor
AU - Papp, Csaba
AU - Nimrichter, Leonardo
AU - Molnár, Gergo
AU - Vágvölgyi, Csaba
AU - Gabaldón, Toni
AU - Nosanchuk, Joshua D.
AU - Gácser, Attila
N1 - Funding Information:
RT and this research was supported by TÁMOP 4.2.4. A/2-11-1-2012-0001 „National Excellence Program – Elaborating and operating an inland student and researcher personal support system convergence program. 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.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-018-19453-4
DO - 10.1038/s41598-018-19453-4
M3 - Article
C2 - 29358719
AN - SCOPUS:85040997609
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 1346
ER -