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REGULATION OF THE RATE OF ASEXUAL GROWTH AND COMMITMENT TO SEXUAL DEVELOPMENT BY DIFFUSIBLE FACTORS FROM IN VITRO CULTURES OF PLASMODIUM FALCIPARUM

The mechanism of switching to sexual differentiation (gametocytogenesis) of Plasmodium falciparum appears to be controlled by stochastic mechanisms that are sensitive to environmental conditions. In any given conditions, only a proportion of genetically identical parasites will become committed to sexual development. We used an experimental co-culture system to detect the presence of diffusible molecules from asexually replicating bloodstream stages of P. falciparum that were capable of influencing the growth and differentiation of the parasite. We cultured two populations of P. falciparum in a shared environment separated by a membrane that allowed free diffusion of molecules. The data presented show that P. falciparum parasites in culture stimulate their own growth and replication, and constitutively inhibit sexual conversion via diffusible molecules. These observations support the model that for P. falciparum, the sexual pathway of development is the default, and that constitutive repression of the sexual pathway permits asexual multiplication to occur in the bloodstream of the human host.

Received March 11, 2002. Accepted for publication January 3, 2003.

Acknowledgments: We are grateful to Dr. Barry Elford for help with the growth assays and to Dr. Crystl Donnelly, Dr. Andrew Roddam, and Emily Lyons for advice with statistical analysis. We also thank the reviewers of this manuscript and Dr. Richard Carter for their useful comments, and Dr. Clare McNulty for her editorial assistance.

Financial support: This work was supported by a Wellcome Trust Program grant awarded to Karen P. Day.

Authors’ address: Mike Dyer and Karen P. Day, Peter Medawar Building for Pathogen Research, Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3SY, United Kingdom.

Reprint requests: Mike Dyer, Peter Medawar Building for Pathogen Research, Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3SY, United Kingdom, Telephone: 44-1865-281-047, Fax: 44-1865-281-245, E-mail: mike.dyer{at}zoology.oxford.ac.uk

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