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.