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.

Development of Leishmania (Leishmania) infantum chagasi in Its Natural Sandfly Vector Lutzomyia longipalpis

“…Transformed promastigotes inside the sandfly gut have to overcome potentially lethal conditions; for example, approximately 50% of L. major ingested by Phlebotomus papatasi during initial infection died during this early stage. 7 Borovsky and Schlein 6 suggested that trypsin-like activity in the midgut of the P. papatasi prevented survival of L. donovani. Pimenta and others 7 observed that the midgut environment, in the first few hours after blood feeding, is harmful even for a strain of L. major that is capable of complete development in the sandfly.…”

“…After the sandfly has had an infected blood meal, ingested amastigotes (non-flagellate forms) differentiate into dividing promastigotes (flagellate forms) to establish the parasite life cycle. However, there are numerous adverse conditions to overcome in the midgut of the host, including digestive enzyme activities 6 and the synthesis of a physical barrier (the peritrophic matrix; PM), 7 and the need to bind to the midgut cells 8,9 to avoid excretion. Lipophosphoglycan, the major Leishmania surface glycoconjugate, protects the parasites from the enzyme activities of its host and mediates parasite attachment to the midgut of the sandfly.…”

Derris (Lonchocarpus) urucu (Leguminosae) Extract Modifies the Peritrophic Matrix Structure of Aedes aegypti (Diptera:Culicidae)

“…A novel role for the PM is suggested. It may provides protection to Leishmania parasite from the action of the host digestive enzymes (Pimenta et al 1997). It also protects the insects, at least partially, against chemical attack by potentially toxic agents with much smaller molecular dimensions (Peters 1992, Regev et al 1996, Lehane 1997, Barbehenn & Martin 1997.…”

Molecular crosstalks inLeishmania-sandfly-host relationships

“…Initially, a blood meal containing aflagellated amastigotes is quickly surrounded by peritrophic matrix, a chitinous framework with a protein-carbohydrate matrix that is secreted by epithelial cells of the midgut (Pimenta et al, 1997). Amastigotes divide and then differentiate into flagellated promastigotes, socalled procyclics.…”

“…Amastigotes divide and then differentiate into flagellated promastigotes, socalled procyclics. During this early stage of development, transforming parasites survive midgut proteases (Schlein & Romano, 1986;Dillon & Lane, 1993;Pimenta et al, 1997;Schlein et al, 1998;Ramalho-Ortigao et al, 2003) and antimicrobial peptides (Boulanger et al, 2004). The peritrophic matrix decays within a few days, the promastigotes escape from the endoperitrophic space and transform to long nectomonad stages.…”