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Proc Natl Acad Sci U S A. May 1, 1993; 90(9): 4266–4270.

Transmission-blocking activity of a chitinase inhibitor and activation of malarial parasite chitinase by mosquito protease.


During development in the mosquito midgut, malarial parasites must traverse a chitin-containing peritrophic matrix (PM) that forms around the food bolus. Previously Huber et al. [Huber, M., Cabib, E. & Miller, L. H. (1991) Proc. Natl. Acad. Sci. USA 88, 2807-2810] reported that the parasite secretes a protein with chitinase activity, and they suggested that parasite chitinase (EC plays an important role in the parasite's egress from the blood meal. We found that allosamidin, a specific inhibitor of chitinase, completely blocked oocyst development in vivo and thus blocked malaria parasite transmission. Addition of exogenous chitinase to the blood meal prevented the PM from forming and reversed the transmission-blocking activity of allosamidin. Using exogenous chitinase, we also found that the PM does not limit the number of parasites that develop into oocysts, suggesting that the parasite produces sufficient quantities of chitinase to penetrate this potential barrier. In addition, we found that treatment of parasite chitinase with a diisopropyl fluorophosphate-sensitive trypsinlike protease from the mosquito midgut or endoproteinase Lys-C increased its enzymatic activity. These results suggest that malaria parasite has evolved an intricate mechanism to adapt to the PM and the protease-rich environment of the mosquito midgut.

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Selected References

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  • Richards AG, Richards PA. The peritrophic membranes of insects. Annu Rev Entomol. 1977;22:219–240. [PubMed]
  • Perrone JB, Spielman A. Microfilarial perforation of the midgut of a mosquito. J Parasitol. 1986 Oct;72(5):723–727. [PubMed]
  • Sieber KP, Huber M, Kaslow D, Banks SM, Torii M, Aikawa M, Miller LH. The peritrophic membrane as a barrier: its penetration by Plasmodium gallinaceum and the effect of a monoclonal antibody to ookinetes. Exp Parasitol. 1991 Feb;72(2):145–156. [PubMed]
  • Huber M, Cabib E, Miller LH. Malaria parasite chitinase and penetration of the mosquito peritrophic membrane. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2807–2810. [PMC free article] [PubMed]
  • Gooday GW, Brydon LJ, Chappell LH. Chitinase in female Onchocerca gibsoni and its inhibition by allosamidin. Mol Biochem Parasitol. 1988 Jun;29(2-3):223–225. [PubMed]
  • Schlein Y, Jacobson RL, Shlomai J. Chitinase secreted by Leishmania functions in the sandfly vector. Proc Biol Sci. 1991 Aug 22;245(1313):121–126. [PubMed]
  • Kaushal DC, Carter R, Rener J, Grotendorst CA, Miller LH, Howard RJ. Monoclonal antibodies against surface determinants on gametes of Plasmodium gallinaceum block transmission of malaria parasites to mosquitoes. J Immunol. 1983 Nov;131(5):2557–2562. [PubMed]
  • Ifediba T, Vanderberg JP. Complete in vitro maturation of Plasmodium falciparum gametocytes. Nature. 1981 Nov 26;294(5839):364–366. [PubMed]
  • Warburg A, Miller LH. Sporogonic development of a malaria parasite in vitro. Science. 1992 Jan 24;255(5043):448–450. [PubMed]
  • Dickinson K, Keer V, Hitchcock CA, Adams DJ. Microsomal chitinase activity from Candida albicans. Biochim Biophys Acta. 1991 Jan 23;1073(1):177–182. [PubMed]
  • Graf R, Raikhel AS, Brown MR, Lea AO, Briegel H. Mosquito trypsin: immunocytochemical localization in the midgut of blood-fed Aedes aegypti (L.). Cell Tissue Res. 1986;245(1):19–27. [PubMed]

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