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Infection and Immunity, June 2001, p. 4041-4047, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.4041-4047.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Knockout of the Rodent Malaria Parasite Chitinase PbCHT1 Reduces Infectivity to Mosquitoes

Johannes T. Dessens,1,* Jacqui Mendoza,1 Charles Claudianos,1 Joseph M. Vinetz,2 Emad Khater,1 Stuart Hassard,1 Gaya R. Ranawaka,1 and Robert E. Sinden1

Department of Biology, Imperial College of Science, Technology, and Medicine, London SW7 2AZ, United Kingdom,1 and WHO Center for Tropical Diseases, University of Texas Medical Branch, Galveston, Texas 77555-06092

Received 9 January 2001/Returned for modification 14 February 2001/Accepted 26 February 2001

During mosquito transmission, malaria ookinetes must cross a chitin-containing structure known as the peritrophic matrix (PM), which surrounds the infected blood meal in the mosquito midgut. In turn, ookinetes produce multiple chitinase activities presumably aimed at disrupting this physical barrier to allow ookinete invasion of the midgut epithelium. Plasmodium chitinase activities are demonstrated targets for human and avian malaria transmission blockade with the chitinase inhibitor allosamidin. Here, we identify and characterize the first chitinase gene of a rodent malaria parasite, Plasmodium berghei. We show that the gene, named PbCHT1, is a structural ortholog of PgCHT1 of the avian malaria parasite Plasmodium gallinaceum and a paralog of PfCHT1 of the human malaria parasite Plasmodium falciparum. Targeted disruption of PbCHT1 reduced parasite infectivity in Anopheles stephensi mosquitoes by up to 90%. Reductions in infectivity were also observed in ookinete feeds---an artificial situation where midgut invasion occurs before PM formation---suggesting that PbCHT1 plays a role other than PM disruption. PbCHT1 null mutants had no residual ookinete-derived chitinase activity in vitro, suggesting that P. berghei ookinetes express only one chitinase gene. Moreover, PbCHT1 activity appeared insensitive to allosamidin inhibition, an observation that raises questions about the use of allosamidin and components like it as potential malaria transmission-blocking drugs. Taken together, these findings suggest a fundamental divergence among rodent, avian, and human malaria parasite chitinases, with implications for the evolution of Plasmodium-mosquito interactions.

* Corresponding author. Mailing address: Department of Biology, Imperial College of Science, Technology, and Medicine, Sir Alexander Fleming Building, Imperial College Rd., London SW7 2AZ, United Kingdom. Phone: 44 20 75945350. Fax: 44 20 75945424. E-mail: j.dessens{at}ic.ac.uk.

Infection and Immunity, June 2001, p. 4041-4047, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.4041-4047.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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