Blocking malaria parasite invasion of mosquito salivary glands

Abstract

The development of malaria parasites in mosquitoes involves significant interactions of the pathogens with host tissues. As detailed by other authors in this volume, ookinetes must successfully negotiate the midgut environment by avoiding digestive enzymes and the developing peritrophic matrix to penetrate and lodge at the basal surface of the midgut epithelium. The resulting oocysts must avoid the host immune responses as the sporozoites develop within. Finally, the sporozoites must navigate the open circulatory system, avoiding humoral and cellular immune responses, to reach and invade their final destination in the mosquito host, the salivary glands. The specificity of these parasite-vector interactions makes them attractive targets for those working to develop synthetic refractory mechanisms in mosquitoes. Some years ago, we proposed to block malaria transmission by interfering with sporozoites in salivary glands (James et al., 1989). This could be achieved by disabling parasites once they invaded the salivary glands, or by blocking the initial invasion. As the tools for testing this strategy have evolved over the last few years, the focus has shifted from the former to the latter approach. Mosquito salivary glandsThe salivary glands of adult mosquitoes are sexually dimorphic and it is clear that the structural and functional differences between the male and female organs reflect the ability of the latter to engage successfully in hematophagy (James, 1994;Stark and James, 1996). The glands are paired structures and are much larger in females than in males (Fig.·1). Each gland consists of three lobes that are attached to a common salivary duct. The duct in culicine mosquitoes extends the length of each lobe, whereas in anophelines, it extends only part-way along the lobe. Each lobe comprises a secretory epithelium surrounding a duct into which saliva is released. The cells in each lobe are organized into a singlelayer epithelium with characteristic basal and apical surfaces. The basal ends of the epithelial cells form the outside surface of the glands and are in contact with a basement membrane that provides the cohesiveness of the glands.In general, the three lobes of male salivary glands appear similar to one another and likely all have the same secretory capabilities (James, 1994). Female glands are differentiated into two lateral and one medial lobes. The proximal regions of the lateral lobes in females express and secrete salivary gland products such as amylases and α1-4 glucosidase that are involved in sugar feeding, and these lobes appear to overlap functionally the male salivary glands (James, 1994;Arcá et al., 1999). In contrast, the medial lobe and distal-lateral lobes express genes whose products such as apyrases, anticoagulants and vasodilatory agents are involved in hematophagy (Champagne et al., 1995;Smartt et al., 1995;Beerntsen et al., 1999;Stark and James, 1998;Arcá et al., 1999).In addition to their gene expression characteristics, the surface properties of the different salivary gland lobes...

Development of Transgenic Fungi That Kill Human Malaria Parasites in Mosquitoes

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Effect of larval crowding on mating competitiveness of Anopheles gambiae mosquitoes

“…This finding, therefore, may help to overcome some of the mating-related hurdles that impeded early genetic control trials [24]. This proposes that, the fitness of all current genetically modified Anopheles constructs [17,19] be re-assayed after under ideal larval conditions in order to show how substantially ecological manipulation could increase their mating success relative to the wild type.…”

“…One promising new control prospect is the possibility of rendering wild vector populations less susceptible to infection by releasing mosquitoes that are genetically modified to resist infection [17-19], or sterile males that will mate with wild females and stop them from reproducing [20]. In the case of a genetically modified mosquito (GMM) strategy, malaria could be reduced by fixing a resistance gene in vector populations, [21-23], and in the case of sterile male release, malaria could be cut by a collapse in the vector population due to a high frequency of unviable matings.…”

Mutant Mos1 mariner transposons are hyperactive in Aedes aegypti

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