The cyclic AMP phosphodiesterase RegA critically regulates encystation in social and pathogenic amoebas

Qingyou Du, Christina Schilde, Elin Birgersson, Zhi-Hui Chen, Stuart McElroy, Pauline Schaap (Lead / Corresponding author)

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    16 Citations (Scopus)
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    Abstract

    Amoebas survive environmental stress by differentiating into encapsulated cysts. As cysts, pathogenic amoebas resist antibiotics, which particularly counteracts treatment of vision-destroying Acanthamoeba keratitis. Limited genetic tractability of amoeba pathogens has left their encystation mechanisms unexplored. The social amoeba Dictyostelium discoideum forms spores in multicellular fruiting bodies to survive starvation, while other dictyostelids, such as Polysphondylium pallidum can additionally encyst as single cells. Sporulation is induced by cAMP acting on PKA, with the cAMP phosphodiesterase RegA critically regulating cAMP levels. We show here that RegA is deeply conserved in social and pathogenic amoebas and that deletion of the RegA gene in P. pallidum causes precocious encystation and prevents cyst germination. We heterologously expressed and characterized Acanthamoeba RegA and performed a compound screen to identify RegA inhibitors. Two effective inhibitors increased cAMP levels and triggered Acanthamoeba encystation. Our results show that RegA critically regulates Amoebozoan encystation and that components of the cAMP signalling pathway could be effective targets for therapeutic intervention with encystation.
    Original languageEnglish
    Pages (from-to)453-459
    Number of pages7
    JournalCellular Signalling
    Volume26
    Issue number2
    DOIs
    Publication statusPublished - Feb 2014

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