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

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...

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Detalhes bibliográficos
Autores: Tóth, Renáta, Cabral, Vitor, Thuer, Ernst, 1986-, Bohner, Flóra, Németh, Tibor, Papp, Csaba, Nimrichter, Leonardo, Molnár, Gergő, Vágvölgyi, Csaba, Gabaldón Estevan, Juan Antonio, 1973-, Nosanchuk, Joshua D., Gácser, Attila
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/43122
Acesso em linha:http://hdl.handle.net/10230/43122
http://dx.doi.org/10.1038/s41598-018-19453-4
Access Level:acceso abierto
Palavra-chave:Fungal immune evasion
Fungal pathogenesis
Descrição
Resumo: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.