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

Hin Siong Chong, Leona Campbell, Matthew P. Padula, Cameron Hill, Elizabeth Harry, Simone S. Li, Marc R. Wilkins, Ben Herbert, Dee Carter*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Article numbere42835
    Pages (from-to)1-10
    Number of pages10
    JournalPLoS ONE
    Volume7
    Issue number8
    DOIs
    Publication statusPublished - 6 Aug 2012

    Fingerprint Dive into the research topics of 'Time-course proteome analysis reveals the dynamic response of cryptococcus gattii cells to fluconazole'. Together they form a unique fingerprint.

    Cite this