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Molecular and Cellular Biology, February 1999, p. 967-978, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Isolation and Functional Characterization of Two Distinct Sexual-Stage-Specific Promoters of the Human Malaria Parasite Plasmodium falciparumdagger

Koen J. Dechering,1,Dagger Anita M. Kaan,1 Wilfred Mbacham,2 Dyann F. Wirth,2 Wijnand Eling,3 Ruud N. H. Konings,1 and Hendrik G. Stunnenberg1,*

Department of Molecular Biology, University of Nijmegen, 6525 ED Nijmegen,1 and Department of Medical Parasitology, University of Nijmegen, 6500 HB Nijmegen,3 The Netherlands, and Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts 021152

Received 10 July 1998/Returned for modification 23 September 1998/Accepted 11 November 1998

Transmission of malaria depends on the successful development of the sexual stages of the parasite within the midgut of the mosquito vector. The differentiation process leading to the production of the sexual stages is delineated by several developmental switches. Arresting the progression through this sexual differentiation pathway would effectively block the spread of the disease. The successful development of such transmission-blocking agents is hampered by the lack of a detailed understanding of the program of gene expression that governs sexual differentiation of the parasite. Here we describe the isolation and functional characterization of the Plasmodium falciparum pfs16 and pfs25 promoters, whose activation marks the developmental switches executed during the sexual differentiation process. We have studied the differential activation of the pfs16 and pfs25 promoters during intraerythrocytic development by transfection of P. falciparum and during gametogenesis and early sporogonic development by transfection of the related malarial parasite P. gallinaceum. Our data indicate that the promoter of the pfs16 gene is activated at the onset of gametocytogenesis, while the activity of the pfs25 promoter is induced following the transition to the mosquito vector. Both promoters have unusual DNA compositions and are extremely A/T rich. We have identified the regions in the pfs16 and pfs25 promoters that are essential for high transcriptional activity. Furthermore, we have identified a DNA-binding protein, termed PAF-1, which activates pfs25 transcription in the mosquito midgut. The data presented here shed the first light on the details of processes of gene regulation in the important human pathogen P. falciparum.

* Corresponding author. Mailing address: Department of Molecular Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands. Phone: 31-24-3653431. Fax: 31-24-3652938. E-mail: stunnenb{at}sci.kun.nl.

Dagger Present address: N.V. Organon, 5340 BH Oss, The Netherlands.

dagger We dedicate this paper to the memory of the late Ruud Konings.

Molecular and Cellular Biology, February 1999, p. 967-978, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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