Importance of polyphosphate in the Leishmania life cycle

Authors:

Kid Kohl1, Haroun Zangger1, Matteo Rossi1, Nathalie Isorce1, Lon-Fye Lye2, Katherine L. Owens2, Stephen M. Beverley2, Andreas Mayer1 and Nicolas Fasel1

doi: 10.15698/mic2018.08.642
Volume 5, pp. 371 to 384, published 22/06/2018.

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Affiliations:

1 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
2 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.

Keywords: 

polyphosphate, VTC4, Leishmania, life cycle, infectivity, temperature stress

Corresponding Author(s):

Nicolas Fasel, Department of Biochemistry, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland; Tel: +41 21 6925732; Fax: +41 21 6925705; nicolas.fasel@unil.ch

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

Kid Kohl, Haroun Zangger, Matteo Rossi, Nathalie Isorce, Lon-Fye Lye, Katherine L. Owens, Stephen M. Beverley, Andreas Mayer and Nicolas Fasel (2018). Importance of Polyphosphate in the Leishmania life cycle. Microbial Cell 5(8): 371-384. doi: 10.15698/mic2018.08.642

© 2018 Kohl et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Protozoan parasites contain negatively charged polymers of a few up to several hundreds of phosphate residues. In other organisms, these polyphosphate (polyP) chains serve as an energy source and phosphate reservoir, and have been implicated in adaptation to stress and virulence of pathogenic organisms. In this study, we confirmed first that the polyP polymerase vacuolar transporter chaperone 4 (VTC4) is responsible for polyP synthesis in Leishmania parasites. During Leishmania in vitro culture, polyP is accumulated in logarithmic growth phase and subsequently consumed once stationary phase is reached. However, polyP is not essential since VTC4-deficient (vtc4–) Leishmania proliferated normally in culture and differentiated into infective metacyclic parasites and into intracellular and axenic amastigotes. In in vivo mouse infections, L. major VTC4 knockout showed a delay in lesion formation but ultimately gave rise to strong pathology, although we were unable to restore virulence by complementation to confirm this phenotype. Knockdown of VTC4 did not alter the course of L. guyanensis infections in mice, suggesting that polyP was not required for infection, or that very low levels of it suffice for lesion development. At higher temperatures, Leishmania promastigotes highly consumed polyP, and both knockdown or deletion of VTC4 diminished parasite survival. Thus, although polyP was not essential in the life cycle of the parasite, our data suggests a role for polyP in increasing parasite survival at higher temperatures, a situation faced by the parasite when transmitted to humans.