Time-course proteome analysis reveals the dynamic response of Cryptococcus gattii cells to fluconazole.

Cryptococcus gattii is an encapsulated fungus capable of causing fatal disease in immunocompetent humans and animals. As current antifungal therapies are few and limited in efficacy, and resistance is an emerging issue, the development of new treatment strategies is urgently required. The current st...

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Autores principales:	Hin Siong Chong, Leona Campbell, Matthew P Padula, Cameron Hill, Elizabeth Harry, Simone S Li, Marc R Wilkins, Ben Herbert, Dee Carter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fabf3a971ac44071a3267be09403e358
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spelling	oai:doaj.org-article:fabf3a971ac44071a3267be09403e3582021-11-18T07:09:31ZTime-course proteome analysis reveals the dynamic response of Cryptococcus gattii cells to fluconazole.1932-620310.1371/journal.pone.0042835https://doaj.org/article/fabf3a971ac44071a3267be09403e3582012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22880118/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Cryptococcus gattii is an encapsulated fungus capable of causing fatal disease in immunocompetent humans and animals. As current antifungal therapies are few and limited in efficacy, and resistance is an emerging issue, the development of new treatment strategies is urgently required. The current study undertook a time-course analysis of the proteome of C. gattii during treatment with fluconazole (FLC), which is used widely in prophylactic and maintenance therapies. The aims were to analyze the overall cellular response to FLC, and to find fungal proteins involved in this response that might be useful targets in therapies that augment the antifungal activity of FLC. During FLC treatment, an increase in stress response, ATP synthesis and mitochondrial respiratory chain proteins, and a decrease in most ribosomal proteins was observed, suggesting that ATP-dependent efflux pumps had been initiated for survival and that the maintenance of ribosome synthesis was differentially expressed. Two proteins involved in fungal specific pathways were responsive to FLC. An integrative network analysis revealed co-ordinated processes involved in drug response, and highlighted hubs in the network representing essential proteins that are required for cell viability. This work demonstrates the dynamic cellular response of a typical susceptible isolate of C. gattii to FLC, and identified a number of proteins and pathways that could be targeted to augment the activity of FLC.Hin Siong ChongLeona CampbellMatthew P PadulaCameron HillElizabeth HarrySimone S LiMarc R WilkinsBen HerbertDee CarterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42835 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hin Siong Chong Leona Campbell Matthew P Padula Cameron Hill Elizabeth Harry Simone S Li Marc R Wilkins Ben Herbert Dee Carter Time-course proteome analysis reveals the dynamic response of Cryptococcus gattii cells to fluconazole.
description	Cryptococcus gattii is an encapsulated fungus capable of causing fatal disease in immunocompetent humans and animals. As current antifungal therapies are few and limited in efficacy, and resistance is an emerging issue, the development of new treatment strategies is urgently required. The current study undertook a time-course analysis of the proteome of C. gattii during treatment with fluconazole (FLC), which is used widely in prophylactic and maintenance therapies. The aims were to analyze the overall cellular response to FLC, and to find fungal proteins involved in this response that might be useful targets in therapies that augment the antifungal activity of FLC. During FLC treatment, an increase in stress response, ATP synthesis and mitochondrial respiratory chain proteins, and a decrease in most ribosomal proteins was observed, suggesting that ATP-dependent efflux pumps had been initiated for survival and that the maintenance of ribosome synthesis was differentially expressed. Two proteins involved in fungal specific pathways were responsive to FLC. An integrative network analysis revealed co-ordinated processes involved in drug response, and highlighted hubs in the network representing essential proteins that are required for cell viability. This work demonstrates the dynamic cellular response of a typical susceptible isolate of C. gattii to FLC, and identified a number of proteins and pathways that could be targeted to augment the activity of FLC.
format	article
author	Hin Siong Chong Leona Campbell Matthew P Padula Cameron Hill Elizabeth Harry Simone S Li Marc R Wilkins Ben Herbert Dee Carter
author_facet	Hin Siong Chong Leona Campbell Matthew P Padula Cameron Hill Elizabeth Harry Simone S Li Marc R Wilkins Ben Herbert Dee Carter
author_sort	Hin Siong Chong
title	Time-course proteome analysis reveals the dynamic response of Cryptococcus gattii cells to fluconazole.
title_short	Time-course proteome analysis reveals the dynamic response of Cryptococcus gattii cells to fluconazole.
title_full	Time-course proteome analysis reveals the dynamic response of Cryptococcus gattii cells to fluconazole.
title_fullStr	Time-course proteome analysis reveals the dynamic response of Cryptococcus gattii cells to fluconazole.
title_full_unstemmed	Time-course proteome analysis reveals the dynamic response of Cryptococcus gattii cells to fluconazole.
title_sort	time-course proteome analysis reveals the dynamic response of cryptococcus gattii cells to fluconazole.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/fabf3a971ac44071a3267be09403e358
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Time-course proteome analysis reveals the dynamic response of Cryptococcus gattii cells to fluconazole.

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