Antibody-mediated inhibition of the growth of larvae from an insect causing cutaneous myiasis in a mammalian host

Abstract

Many insects feed on blood or tissue from mammalian hosts. One potential strategy for the control of these insects is to vaccinate the host with antigens derived from the insect. The larvae of the f ly Lucilia cuprina feed on ovine tissue and tissue f luids causing a cutaneous myiasis associated with considerable host morbidity and mortality. A candidate vaccine antigen, peritrophin 95, was purified from the peritrophic membrane, which lines the gut of these larvae. Serum from sheep vaccinated with peritrophin 95 inhibited growth of first-instar L. cuprina larvae that fed on this serum. Growth inhibition was probably caused by antibody-mediated blockage of the normally semipermeable peritrophic membrane and the subsequent development of an impervious layer of undefined composition on the gut lumen side of the peritrophic membrane that restricted access of nutrients to the larvae. The amino acid sequence of peritrophin 95 was determined by cloning the DNA complementary to its mRNA. The deduced amino acid sequence codes for a secreted protein containing a distinct Cys-rich domain of 317 amino acids followed by a mucin-like domain of 139 amino acids. The Cys-rich domain may be involved in binding chitin. This report describes a novel immunological strategy for the potential control of L. cuprina larvae that may have general application to the control of other insect pests.Many insects feed on blood, tissue, or tissue fluids of mammals. The insect feeding process itself is often detrimental to the host and in addition many of these insects are vectors for the transmission of viral, protozoal, and helminth parasites that cause considerable host morbidity and mortality, particularly in humans and livestock animals. Current strategies for control of insect pests in livestock industries are becoming inadequate because of rapid and widespread development of insecticide resistance and concerns relating to the presence of chemical residues derived from these insecticides in livestock products and the immediate environment. Thus, alternative means of controlling these insects are required.One possible approach is to vaccinate the host against the offending insect life stage by using an insect gut antigen (1, 2). The gut of most insects is lined with a peritrophic membrane (PM or peritrophic matrix) at least at some stage in the life cycle (3). This semipermeable membrane is composed of chitin, proteoglycans, and proteins. The functions of the PM involve facilitating the digestive process and protecting the gut epithelial cells from invasion by microrganisms and parasites (3). The permeability of the PM is such that it either excludes or severely restricts access of ingested host antibodies to the underlying digestive epithelial cells of the gut (3, 4). The PM, however, is bathed in ingested host antibodies and, therefore, PM proteins may be candidate vaccine antigens. Preliminary studies have shown that sheep vaccinated with crude PM protein extracts from the larvae of the fly Lucilia cuprina induce an anti-larval i...

Identification and characterization of two chitin‐binding proteins from the peritrophic membrane of the silkworm, Bombyx mori L.

“…A number of PM proteins may be associated with this process and a few of them have the chitin-binding activity. The activity was attributed to their peritrophin domains (Elvin et al, 1996;Casu et al, 1997;Schorderet et al, 1998;Tellam et al, 1999;Wijffels et al, 2001;Tellam et al, 2003). In this study, we identified two chitin-binding proteins, BmPM-P43 and BmPM-P41, containing a polysaccharide deacetylase domain, different from the proteins containing peritrophin domains.…”

“…Several peritrophins were identified: Peritrophin-44 and peritrophin-48 were purified from 6 M urea extract of Lucilia cuprina PM (Elvin et al, 1996;Schorderet et al, 1998); Ag-Aper1, from blood-fed adult female Anopheles gambiae (Shen and Jacobs-Lorena, 1998); Peritrophin-95 be purified from L. cuprina (Casu et al, 1997) etc. These PM proteins have the peritrophin domains, which contain 65-70 amino acid residues and are characterized by a conserved register of six cysteine residues C-X 13-20 CX 5-6 CX 9-19 -CX 10-14 CX 4-14 C (X is not cysteine) called the peritrophin-A domain and a few aromatic amino acid residues .…”

A cell surface mucin specifically expressed in the midgut of the malaria mosquito Anopheles gambiae

“…The peritrophic matrix is an extracellular sac, composed of chitin, proteins, and proteoglycans (2,3), which completely surrounds the ingested food and is secreted by the gut epithelial cells. All the recently cloned peritrophic matrix proteins from Lucilia cuprina (5,6), Trichoplusia ni (7), and the mosquito Anopheles gambiae (8) have at least two chitinbinding domains that are presumed to function in the crosslinking of the chitin fibrils. However, some of these proteins also have mucin-like domains (6,7), suggesting that the insect peritrophic matrix resembles the vertebrate intestinal mucus, a structure largely composed of mucins.…”

“…All the recently cloned peritrophic matrix proteins from Lucilia cuprina (5,6), Trichoplusia ni (7), and the mosquito Anopheles gambiae (8) have at least two chitinbinding domains that are presumed to function in the crosslinking of the chitin fibrils. However, some of these proteins also have mucin-like domains (6,7), suggesting that the insect peritrophic matrix resembles the vertebrate intestinal mucus, a structure largely composed of mucins. In addition to providing protection, the peritrophic matrix may also facilitate digestion by compartmentalization of digestive enzymes (9).…”

Deterministic Modeling of Negative Cross-resistance Strategies for use in Transgenic Host-plant Resistance

“…Resistance factors deployed, or considered for use, in host-plant resistance include Bt -endotoxin, protease inhibitors, -amylase inhibitors (Shade et al, 1994), Photorhabdus luminescens proteins (Roush, 1998), Helicoverpa stunt virus (Schuler et al, 1998), antibodies (Casu et al, 1997), and lectins (Pittendrigh et al, 1997;ZhuSalzman et al, 1998). Some of aforementioned resistance factors are currently in the process of being developed for transformation into plants.…”