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Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito

Author

Listed:
  • O. Billker

    (Imperial College)

  • V. Lindo

    (Imperial College)

  • M. Panico

    (Imperial College)

  • A. E. Etienne

    (Imperial College)

  • T. Paxton

    (Imperial College)

  • A. Dell

    (Imperial College)

  • M. Rogers

    (M-Scan Inc.)

  • R. E. Sinden

    (Imperial College)

  • H. R. Morris

    (Imperial College)

Abstract

Malaria is transmitted from vertebrate host to mosquito vector by mature sexual blood-living stages called gametocytes1,2. Within seconds of ingestion into the mosquito bloodmeal, gametocytes undergo gametogenesis. Induction requires the simultaneous exposure to at least two stimuli in vitro: a drop in bloodmeal temperature to 5 °C below that of the vertebrate host1,2,3, and a rise in pH from 7.4 to 8.0–8.2 (refs 1, 4). In vivo the mosquito bloodmeal has a pH of between 7.5 and 7.6 (refs 5, 6). It is thought that in vivo the second inducer is an unknown mosquito-derived gametocyte-activating factor5,7,8. Here we show that this factor is xanthurenic acid. We also show that low concentrations of xanthurenic acid can act together with pH to induce gametogenesis in vitro. Structurally related compounds are at least ninefold less effective at inducing gametogenesis in vitro. In Drosophila mutants with lesions in the kynurenine pathway of tryptophan metabolism (of which xanthurenic acid is a side product), no alternative active compound was detected in crude insect homogenates. These data could form the basis of the rational development of new methods of interrupting the transmission of malaria using drugs or new refractory mosquito genotypes to block parasite gametogenesis.

Suggested Citation

  • O. Billker & V. Lindo & M. Panico & A. E. Etienne & T. Paxton & A. Dell & M. Rogers & R. E. Sinden & H. R. Morris, 1998. "Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito," Nature, Nature, vol. 392(6673), pages 289-292, March.
    • Handle: RePEc:nat:nature:v:392:y:1998:i:6673:d:10.1038_32667
    DOI: 10.1038/32667
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    Cited by:

    1. Ravish Rashpa & Natacha Klages & Domitille Schvartz & Carla Pasquarello & Mathieu Brochet, 2023. "The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Jiepeng Guan & Peijia Wu & Xiaoli Mo & Xiaolong Zhang & Wenqi Liang & Xiaoming Zhang & Lubin Jiang & Jian Li & Huiting Cui & Jing Yuan, 2024. "An axonemal intron splicing program sustains Plasmodium male development," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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