Importance of polyphosphate in the Leishmania life cycle
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 organi...
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| Format: | Article |
| Language: | English |
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Shared Science Publishers OG
2018-06-01
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| Series: | Microbial Cell |
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| Online Access: | http://microbialcell.com/researcharticles/importance-of-polyphosphate-in-the-leishmania-life-cycle/ |
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| author | Kid Kohl Haroun Zangger Matteo Rossi Nathalie Isorce Lon-Fye Lye Katherine L. Owens Stephen M. Beverley Andreas Mayer Nicolas Fasel |
| author_facet | Kid Kohl Haroun Zangger Matteo Rossi Nathalie Isorce Lon-Fye Lye Katherine L. Owens Stephen M. Beverley Andreas Mayer Nicolas Fasel |
| author_sort | Kid Kohl |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T13:27:22Z |
| format | Article |
| id | doaj.art-929961d5bd494cdbbbe7595c49e4de7c |
| institution | Directory Open Access Journal |
| issn | 2311-2638 |
| language | English |
| last_indexed | 2024-12-20T13:27:22Z |
| publishDate | 2018-06-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Microbial Cell |
| spelling | doaj.art-929961d5bd494cdbbbe7595c49e4de7c2022-12-21T19:39:14ZengShared Science Publishers OGMicrobial Cell2311-26382018-06-015837138410.15698/mic2018.08.642Importance of polyphosphate in the Leishmania life cycleKid Kohl0Haroun Zangger1Matteo Rossi2Nathalie Isorce3Lon-Fye Lye4Katherine L. Owens5Stephen M. Beverley6Andreas Mayer7Nicolas Fasel8Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.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.http://microbialcell.com/researcharticles/importance-of-polyphosphate-in-the-leishmania-life-cycle/polyphosphateVTC4Leishmanialife cycleinfectivitytemperature stress |
| spellingShingle | Kid Kohl Haroun Zangger Matteo Rossi Nathalie Isorce Lon-Fye Lye Katherine L. Owens Stephen M. Beverley Andreas Mayer Nicolas Fasel Importance of polyphosphate in the Leishmania life cycle Microbial Cell polyphosphate VTC4 Leishmania life cycle infectivity temperature stress |
| title | Importance of polyphosphate in the Leishmania life cycle |
| title_full | Importance of polyphosphate in the Leishmania life cycle |
| title_fullStr | Importance of polyphosphate in the Leishmania life cycle |
| title_full_unstemmed | Importance of polyphosphate in the Leishmania life cycle |
| title_short | Importance of polyphosphate in the Leishmania life cycle |
| title_sort | importance of polyphosphate in the leishmania life cycle |
| topic | polyphosphate VTC4 Leishmania life cycle infectivity temperature stress |
| url | http://microbialcell.com/researcharticles/importance-of-polyphosphate-in-the-leishmania-life-cycle/ |
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