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 - 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 -