title: A novel role for the peritrophic matrix in protecting Leishmania from the hydrolytic activities of the sand fly midgut.
abstract: The role of the peritrophic matrix (PM) in the development of Leishmania major infections in a natural vector, Phlebotomus papatasi, was investigated by addition of exogenous chitinase to the bloodmeal, which completely blocked PM formation. Surprisingly, the absence of the PM was associated with the loss of midgut infections. The chitinase was not directly toxic to the parasite, nor were midgut infections lost due to premature expulsion of the bloodmeal. Most parasites were killed in chitinase-treated flies within the first 4 h after feeding. Substantial early killing was also observed in control flies, suggesting that the lack of PM exacerbates lethal conditions which normally exist in the blood-fed midgut. Early parasite mortality was reversed by soybean trypsin inhibitor. Allosamadin, a specific inhibitor of chitinase, led to a thickening of the PM, and also prevented the early parasite mortality seen in infected flies. Susceptibility to gut proteases was extremely high in transitional-stage parasites, while amastigotes and fully transformed promastigotes were relatively resistant. A novel role for the PM in promoting parasite survival is suggested, in which the PM creates a barrier to the rapid diffusion of digestive enzymes, and limits the exposure of parasites to these enzymes during the time when they are especially vulnerable to proteolytic damage.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Pimenta
authors.forename: G B
authors.initials: GB
authors.lastname: Modi
authors.forename: S T
authors.initials: ST
authors.lastname: Pereira
authors.forename: M
authors.initials: M
authors.lastname: Shahabuddin
authors.forename: D L
authors.initials: DL
authors.lastname: Sacks
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002688:Chitinases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004064:Digestive System / Q000033:anatomy & histology / Q000378:metabolism / Q000469:parasitology*; D004435:Eating; D006868:Hydrolysis; D007303:Insect Vectors / Q000033:anatomy & histology / Q000469:parasitology*; D018320:Leishmania major / Q000187:drug effects*; D010691:Phlebotomus / Q000033:anatomy & histology / Q000469:parasitology*; D014312:Trisaccharides / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology*
chemical_list: D014312:Trisaccharides; C054851:allosamidin; D002688:Chitinases; D014357:Trypsin; D000117:Acetylglucosamine