Knockout of the rodent malaria parasite chitinase PbCHT1 reduces infectivity to mosquitoes

Dessens, Johannes T., Mendoza, Jacqui, Claudianos, Charles, Vinetz, Joseph M., Khater, Emad, Hassard, Stuart, Ranawaka, Gaya R. and Sinden, Robert E. (2001) Knockout of the rodent malaria parasite chitinase PbCHT1 reduces infectivity to mosquitoes. Infection And Immunity, 69 6: 4041-4047. doi:10.1128/IAI.69.6.4041-4047.2001

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Author Dessens, Johannes T.
Mendoza, Jacqui
Claudianos, Charles
Vinetz, Joseph M.
Khater, Emad
Hassard, Stuart
Ranawaka, Gaya R.
Sinden, Robert E.
Title Knockout of the rodent malaria parasite chitinase PbCHT1 reduces infectivity to mosquitoes
Journal name Infection And Immunity
ISSN 1098-5522
1070-6313
Publication date 2001-06
Sub-type Article (original research)
DOI 10.1128/IAI.69.6.4041-4047.2001
Open Access Status File (Publisher version)
Volume 69
Issue 6
Start page 4041
End page 4047
Total pages 7
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Abstract 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.
Keyword Immunology
Infectious Diseases
Plasmodium
Transmission
Protease
Midgut
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Wed, 17 Oct 2007, 10:55:18 EST