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Leishmania donovani P23 protects parasites against HSP90 inhibitor-mediated growth arrest

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Cell Stress and Chaperones Aims and scope

Abstract

In Leishmania donovani, the HSP90 chaperone complex plays an essential role in the control of the parasite’s life cycle, general viability and infectivity. Several of the associated co-chaperones were also shown to be essential for viability and/or infectivity to mammalian cells. Here, we identify and describe the co-chaperone P23 and distinguish its function from that of the structurally related small heat shock protein HSP23. P23 is expressed constitutively and associates itself with members of the HSP90 complex, i.e. HSP90 and Sti1. Viable P23 gene replacement mutants could be raised and confirmed as null mutants without deleterious effects on viability under a variety of physiological growth conditions. The null mutant also displays near-wild-type infectivity, arguing against a decisive role played by P23 in laboratory settings. However, the P23 null mutant displays a marked hypersensitivity against HSP90 inhibitors geldanamycin and radicicol. P23 also appears to affect the radicicol resistance of a HSP90 Leu33-Ile mutant described previously. Therefore, the annotation of L. donovani P23 as HSP90-interacting co-chaperone is confirmed.

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Acknowledgments

We thank technical Dorothea Zander and Nicole Rath for expert technical assistance and the members of the laboratory for stimulating discussions.

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  1. Gabi Ommen

    Present address: Euroimmun AG, Seekamp 31, 23560, Lübeck, Germany

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  1. Bernhard Nocht Institute for Tropical Medicine, P.O. Box 30 41 20, 20324, Hamburg, Germany

    Antje Hombach, Gabi Ommen, Victoria Sattler & Joachim Clos

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Hombach, A., Ommen, G., Sattler, V. et al. Leishmania donovani P23 protects parasites against HSP90 inhibitor-mediated growth arrest. Cell Stress and Chaperones 20, 673–685 (2015). https://doi.org/10.1007/s12192-015-0595-y

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