Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum

Nicolas M.B. Brancucci; Joseph P. Gerdt; Cheng Qi Wang; Mariana De Niz; Nisha Philip; Swamy R. Adapa; Min Zhang; Eva Hitz; Igor Niederwieser; Sylwia D. Boltryk; Marie Claude Laffitte; Martha A. Clark; Christof Grüring; Deepali Ravel; Alexandra Blancke Soares; Allison Demas; Selina Bopp; Belén Rubio-Ruiz; Ana Conejo-Garcia; Dyann F. Wirth; Edyta Gendaszewska-Darmach; Manoj T. Duraisingh; John H. Adams; Till S. Voss; Andrew P. Waters; Rays H.Y. Jiang; Jon Clardy; Matthias Marti

doi:10.1016/j.cell.2017.10.020

Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum

Nicolas M.B. Brancucci, Joseph P. Gerdt, Cheng Qi Wang, Mariana De Niz, Nisha Philip, Swamy R. Adapa, Min Zhang, Eva Hitz, Igor Niederwieser, Sylwia D. Boltryk, Marie Claude Laffitte, Martha A. Clark, Christof Grüring, Deepali Ravel, Alexandra Blancke Soares, Allison Demas, Selina Bopp, Belén Rubio-Ruiz, Ana Conejo-Garcia, Dyann F. WirthEdyta Gendaszewska-Darmach, Manoj T. Duraisingh, John H. Adams, Till S. Voss, Andrew P. Waters, Rays H.Y. Jiang, Jon Clardy^*, Matthias Marti

^*Corresponding author for this work

Cell & Developmental Biology

Research output: Contribution to journal › Article › peer-review

216 Scopus citations

Abstract

Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission. The host-derived lipid lysophosphatidylcholine controls Plasmodium falciparum cell fate by repressing parasite sexual differentiation, a key step in malaria transmission.

Original language	English (US)
Pages (from-to)	1532-1544.e15
Journal	Cell
Volume	171
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2017.10.020
State	Published - Dec 14 2017

Funding

We thank C. Ben Mamoun for sharing the anti-PMT antibody and K. Dantzler for critically reading the manuscript. We are grateful to P. Lui and W. Beyer for technical assistance. This work was supported by Senior Investigator Award 172862 and IRS Award 172805 from the Wellcome Trust and a career development award from the Burroughs Wellcome Fund to M.M., NIH grants GM086258 to J.C. and R01RHL139337 to M.T.D., and a Centre Award 104111 to the Wellcome Centre for Molecular Parasitology and Swiss National Science Foundation grants ( 31003A_163258 and BSCGI0_157729 ) to T.S.V. N.M.B.B. and M.D.N. received Postdoc.Mobility fellowships from the Swiss National Science Foundation ( P300PA_160975 and P2BEP3_165396 , respectively). J.P.G. was supported by an NIH NRSA fellowship from the NIGMS ( F32 GM116205 ).

Keywords

Kennedy pathway
Plasmodium falciparum
environmental sensing
lysophosphatidylcholine
malaria
phospholipid metabolism
sexual differentiation
transmission

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2017.10.020

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Brancucci, N. M. B., Gerdt, J. P., Wang, C. Q., De Niz, M., Philip, N., Adapa, S. R., Zhang, M., Hitz, E., Niederwieser, I., Boltryk, S. D., Laffitte, M. C., Clark, M. A., Grüring, C., Ravel, D., Blancke Soares, A., Demas, A., Bopp, S., Rubio-Ruiz, B., Conejo-Garcia, A., ... Marti, M. (2017). Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum. Cell, 171(7), 1532-1544.e15. https://doi.org/10.1016/j.cell.2017.10.020

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title = "Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum",

abstract = "Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission. The host-derived lipid lysophosphatidylcholine controls Plasmodium falciparum cell fate by repressing parasite sexual differentiation, a key step in malaria transmission.",

keywords = "Kennedy pathway, Plasmodium falciparum, environmental sensing, lysophosphatidylcholine, malaria, phospholipid metabolism, sexual differentiation, transmission",

author = "Brancucci, {Nicolas M.B.} and Gerdt, {Joseph P.} and Wang, {Cheng Qi} and {De Niz}, Mariana and Nisha Philip and Adapa, {Swamy R.} and Min Zhang and Eva Hitz and Igor Niederwieser and Boltryk, {Sylwia D.} and Laffitte, {Marie Claude} and Clark, {Martha A.} and Christof Gr{\"u}ring and Deepali Ravel and {Blancke Soares}, Alexandra and Allison Demas and Selina Bopp and Bel{\'e}n Rubio-Ruiz and Ana Conejo-Garcia and Wirth, {Dyann F.} and Edyta Gendaszewska-Darmach and Duraisingh, {Manoj T.} and Adams, {John H.} and Voss, {Till S.} and Waters, {Andrew P.} and Jiang, {Rays H.Y.} and Jon Clardy and Matthias Marti",

note = "Funding Information: We thank C. Ben Mamoun for sharing the anti-PMT antibody and K. Dantzler for critically reading the manuscript. We are grateful to P. Lui and W. Beyer for technical assistance. This work was supported by Senior Investigator Award 172862 and IRS Award 172805 from the Wellcome Trust and a career development award from the Burroughs Wellcome Fund to M.M., NIH grants GM086258 to J.C. and R01RHL139337 to M.T.D., and a Centre Award 104111 to the Wellcome Centre for Molecular Parasitology and Swiss National Science Foundation grants ( 31003A_163258 and BSCGI0_157729 ) to T.S.V. N.M.B.B. and M.D.N. received Postdoc.Mobility fellowships from the Swiss National Science Foundation ( P300PA_160975 and P2BEP3_165396 , respectively). J.P.G. was supported by an NIH NRSA fellowship from the NIGMS ( F32 GM116205 ). Publisher Copyright: {\textcopyright} 2017 The Author(s)",

year = "2017",

month = dec,

day = "14",

doi = "10.1016/j.cell.2017.10.020",

language = "English (US)",

volume = "171",

pages = "1532--1544.e15",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

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Brancucci, NMB, Gerdt, JP, Wang, CQ, De Niz, M, Philip, N, Adapa, SR, Zhang, M, Hitz, E, Niederwieser, I, Boltryk, SD, Laffitte, MC, Clark, MA, Grüring, C, Ravel, D, Blancke Soares, A, Demas, A, Bopp, S, Rubio-Ruiz, B, Conejo-Garcia, A, Wirth, DF, Gendaszewska-Darmach, E, Duraisingh, MT, Adams, JH, Voss, TS, Waters, AP, Jiang, RHY, Clardy, J & Marti, M 2017, 'Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum', Cell, vol. 171, no. 7, pp. 1532-1544.e15. https://doi.org/10.1016/j.cell.2017.10.020

TY - JOUR

T1 - Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum

AU - Brancucci, Nicolas M.B.

AU - Gerdt, Joseph P.

AU - Wang, Cheng Qi

AU - De Niz, Mariana

AU - Philip, Nisha

AU - Adapa, Swamy R.

AU - Zhang, Min

AU - Hitz, Eva

AU - Niederwieser, Igor

AU - Boltryk, Sylwia D.

AU - Laffitte, Marie Claude

AU - Clark, Martha A.

AU - Grüring, Christof

AU - Ravel, Deepali

AU - Blancke Soares, Alexandra

AU - Demas, Allison

AU - Bopp, Selina

AU - Rubio-Ruiz, Belén

AU - Conejo-Garcia, Ana

AU - Wirth, Dyann F.

AU - Gendaszewska-Darmach, Edyta

AU - Duraisingh, Manoj T.

AU - Adams, John H.

AU - Voss, Till S.

AU - Waters, Andrew P.

AU - Jiang, Rays H.Y.

AU - Clardy, Jon

AU - Marti, Matthias

N1 - Funding Information: We thank C. Ben Mamoun for sharing the anti-PMT antibody and K. Dantzler for critically reading the manuscript. We are grateful to P. Lui and W. Beyer for technical assistance. This work was supported by Senior Investigator Award 172862 and IRS Award 172805 from the Wellcome Trust and a career development award from the Burroughs Wellcome Fund to M.M., NIH grants GM086258 to J.C. and R01RHL139337 to M.T.D., and a Centre Award 104111 to the Wellcome Centre for Molecular Parasitology and Swiss National Science Foundation grants ( 31003A_163258 and BSCGI0_157729 ) to T.S.V. N.M.B.B. and M.D.N. received Postdoc.Mobility fellowships from the Swiss National Science Foundation ( P300PA_160975 and P2BEP3_165396 , respectively). J.P.G. was supported by an NIH NRSA fellowship from the NIGMS ( F32 GM116205 ). Publisher Copyright: © 2017 The Author(s)

PY - 2017/12/14

Y1 - 2017/12/14

N2 - Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission. The host-derived lipid lysophosphatidylcholine controls Plasmodium falciparum cell fate by repressing parasite sexual differentiation, a key step in malaria transmission.

AB - Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission. The host-derived lipid lysophosphatidylcholine controls Plasmodium falciparum cell fate by repressing parasite sexual differentiation, a key step in malaria transmission.

KW - Kennedy pathway

KW - Plasmodium falciparum

KW - environmental sensing

KW - lysophosphatidylcholine

KW - malaria

KW - phospholipid metabolism

KW - sexual differentiation

KW - transmission

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UR - http://www.scopus.com/inward/citedby.url?scp=85033401972&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2017.10.020

DO - 10.1016/j.cell.2017.10.020

M3 - Article

C2 - 29129376

AN - SCOPUS:85033401972

SN - 0092-8674

VL - 171

SP - 1532-1544.e15

JO - Cell

JF - Cell

IS - 7

ER -

Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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