Interactions of human malaria parasites, Plasmodium wVaxand P.falciparum, with the midgut of Anopheles mosquitoes (original) (raw)
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Malaria parasite colonisation of the mosquito midgut – Placing the Plasmodium ookinete centre stage
Vector-borne diseases constitute an enormous burden on public health across the world. However, despite the importance of interactions between infectious pathogens and their respective vector for disease transmission, the biology of the pathogen in the insect is often less well understood than the forms that cause human infections. Even with the global impact of Plasmodium parasites, the causative agents of malarial disease, no vaccine exists to prevent infection and resistance to all frontline drugs is emerging. Malaria parasite migration through the mosquito host constitutes a major population bottleneck of the lifecycle and therefore represents a powerful, although as yet relatively untapped, target for therapeutic intervention. The understanding of parasite-mosquito interactions has increased in recent years with developments in genome-wide approaches, genomics and proteomics. Each development has shed significant light on the biology of the malaria parasite during the mosquito phase of the lifecycle. Less well understood, however, is the process of midgut colonisation and oocyst formation, the precursor to parasite re-infection from the next mosquito bite. Here, we review the current understanding of cellular and molecular events underlying midgut colonisation centred on the role of the motile ookinete. Further insight into the major interactions between the parasite and the mosquito will help support the broader goal to identify targets for transmission-blocking therapies against malarial disease. Ó
Multiple pathways for Plasmodium ookinete invasion of the mosquito midgut
Proceedings of the National Academy of Sciences, 2014
Plasmodium ookinete invasion of the mosquito midgut is a crucial step of the parasite life cycle but little is known about the molecular mechanisms involved. Previously, a phage display peptide library screen identified SM1, a peptide that binds to the mosquito midgut epithelium and inhibits ookinete invasion. SM1 was characterized as a mimotope of an ookinete surface enolase and SM1 presumably competes with enolase, the presumed ligand, for binding to a putative midgut receptor. Here we identify a mosquito midgut receptor that binds both SM1 and ookinete surface enolase, termed "enolase-binding protein" (EBP). Moreover, we determined that Plasmodium berghei parasites are heterogeneous for midgut invasion, as some parasite clones are strongly inhibited by SM1 whereas others are not. The SM1-sensitive parasites required the mosquito EBP receptor for midgut invasion whereas the SM1resistant parasites invaded the mosquito midgut independently of EBP. These experiments provide evidence that Plasmodium ookinetes can invade the mosquito midgut by alternate pathways. Furthermore, another peptide from the original phage display screen, midgut peptide 2 (MP2), strongly inhibited midgut invasion by P. berghei (SM1-sensitive and SM1-resistant) and Plasmodium falciparum ookinetes, suggesting that MP2 binds to a separate, universal receptor for midgut invasion.
Journal of Biological Chemistry, 1999
In Plasmodium-infected mosquitoes, oocysts are preferentially located at the posterior half of the posterior midgut. Because mosquitoes rest vertically after feeding, the effect of gravity on the ingested blood has been proposed as the cause of such a biased distribution. In this paper, we examined the oocyst distribution on the midguts of mosquitoes that were continuously rotated to nullify the effect of gravity and found that the typical pattern of oocyst distribution did not change. Invasion of the midgut epithelium by ookinetes was similarly found to be biased toward the posterior part of the posterior midgut. We examined whether the distribution of oocysts depends on the distribution of vesicular ATPase (V-ATPase)-overexpressing cells that Plasmodium ookinetes preferentially use to cross the midgut epithelium. An antiserum raised against recombinant Aedes aegypti V-ATPase B subunit indicated that the majority of V-ATPase-overexpressing cells in Ae. aegypti and Anopheles gambiae are localized at the posterior part of the posterior midgut. We propose that the typical distribution of oocysts on the mosquito midgut is attributable to the presence and the spatial distribution of the V-ATPase-overexpressing cells in the midgut epithelium.
SOAP, a novel malaria ookinete protein involved in mosquito midgut invasion and oocyst development
Molecular Microbiology, 2003
An essential, but poorly understood part of malaria transmission by mosquitoes is the development of the ookinetes into the sporozoite-producing oocysts on the mosquito midgut wall. For successful oocyst formation newly formed ookinetes in the midgut lumen must enter, traverse, and exit the midgut epithelium to reach the midgut basal lamina, processes collectively known as midgut invasion. After invasion ookinete-to-oocyst transition must occur, a process believed to require ookinete interactions with basal lamina components. Here, we report on a novel extracellular malaria protein expressed in ookinetes and young oocysts, named secreted ookinete adhesive protein (SOAP). The SOAP gene is highly conserved amongst Plasmodium species and appears to be unique to this genus. It encodes a predicted secreted and soluble protein with a modular structure composed of two unique cysteine-rich domains. Using the rodent malaria parasite Plasmodium berghei we show that SOAP is targeted to the micronemes and forms high molecular mass complexes via disulphide bonds. Moreover, SOAP interacts strongly with mosquito laminin in yeast-two-hybrid assays. Targeted disruption of the SOAP gene gives rise to ookinetes that are markedly impaired in their ability to invade the mosquito midgut and form oocysts. These results identify SOAP as a key molecule for ookinete-to-oocyst differentiation in mosquitoes.
Plasmodium invasion of mosquito cells: hawk or dove
Trends in Parasitology, 2001
In the past five years, there has been renewed interest in the early development of the malaria parasite in the mosquito. Numerous exciting studies have examined in more detail the cellular and molecular interactions of the ookinete with the peritrophic matrix, midgut epithelium and basal lamina of the mosquito midgut, and a plethora of new responses by the mosquito to this invasion process have been described.
Malaria journal, 2005
P25 and P28 are related ookinete surface proteins highly conserved throughout the Plasmodium genus that are under consideration as candidates for inclusion in transmission-blocking vaccines. Previous research using transgenic rodent malaria parasites lacking P25 and P28 has demonstrated that these proteins have multiple partially redundant functions during parasite infection of the mosquito vector, including an undefined role in ookinete traversal of the mosquito midgut epithelium, and it has been suggested that, unlike wild-type parasites, Dko P25/P28 parasites migrate across the midgut epithelium via an intercellular, rather than intracellular, route. This paper presents an alternative interpretation for the previous observations of Dko P25/P28 parasites, based upon a recently published model of the route of ookinete invasion across the midgut epithelium. This model claims ookinete invasion is intracellular, with entry occurring through the lateral apical plasma membrane of midgut...
Plasmodium ookinetes coopt mammalian plasminogen to invade the mosquito midgut
Proceedings of the National Academy of Sciences, 2011
Ookinete invasion of the mosquito midgut is an essential step for the development of the malaria parasite in the mosquito. Invasion involves recognition between a presumed mosquito midgut receptor and an ookinete ligand. Here, we show that enolase lines the ookinete surface. An antienolase antibody inhibits oocyst development of both Plasmodium berghei and Plasmodium falciparum, suggesting that enolase may act as an invasion ligand. Importantly, we demonstrate that surface enolase captures plasminogen from the mammalian blood meal via its lysine motif (DKSLVK) and that this interaction is essential for midgut invasion, because plasminogen depletion leads to a strong inhibition of oocyst formation. Although addition of recombinant WT plasminogen to depleted serum rescues oocyst formation, recombinant inactive plasminogen does not, thus emphasizing the importance of plasmin proteolytic activity for ookinete invasion. The results support the hypothesis that enolase on the surface of Plasmodium ookinetes plays a dual role in midgut invasion: by acting as a ligand that interacts with the midgut epithelium and, further, by capturing plasminogen, whose conversion to active plasmin promotes the invasion process.
Mosquito midgut glycoproteins and recognition sites for malaria parasites
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1997
Midgut glycoproteins of the malaria vector Anopheles tessellatus were partially characterised by gel electrophoresis and Ž . Ž . lectin binding. Specific binding to wheat germ agglutinin WGA and Concanavalin A Con A indicated the presence of N-linked core oligosaccharides in many proteins. Rabbit antibodies were produced against wheat germ agglutinin binding Ž . proteins WGABP . These antibodies also recognised distinct proteins in the peritrophic membrane which is secreted into the midgut to enclose a bloodmeal. Rabbit anti-WGABP antibodies ingested in a bloodmeal containing infective gametocytes of the human malaria parasites Plasmodium falciparum and P. ÕiÕax tended to reduce infectivity of the parasites to vector mosquitoes. Chitotriose added to a bloodmeal also inhibited parasite development in the mosquito. The results are consistent with a hypothesis that N-acetyl glucosamine residues in mosquito midgut glycoproteins andror midgut chitin and proteoglycan function as recognition sites for malaria parasites. q 1997 Elsevier Science B.V.
Malaria-induced apoptosis in mosquito ovaries: a mechanism to control vector egg production
Journal of …, 2001
Fecundity reduction is a life-history trait commonly associated with parasitized molluscs and arthropods (Hurd, 1990). It is thought to occur as a result of a trade-off in host resource management between demands made by the parasite and those required for egg production (Obrebski, 1975; Read, 1990). Complete castration rarely occurs and, in insects in particular, some temporary or permanent curtailment of egg production is most common (Hurd, 1993). Although there are numerous reports of the effect of parasites on insect reproductive success, our understanding of the mechanisms that initiate and control fecundity reduction is poor. We are currently examining the effects of malaria on various aspects of oogenesis in the major vectors of human malaria Anopheles stephensi and Anopheles gambiae. Malaria is regarded as the most serious of the parasitic diseases, causing 300-500 million clinical cases and 1.5-2.7 million deaths annually (www.who.org). It is caused by protozoans of the genus Plasmodium and is transmitted by anopheline mosquitoes during blood feeding. Within 24 h of ingestion, Plasmodium spp. gametes are fertilised in the blood bolus within the mosquito midgut, and motile ookinetes, developed from zygotes, begin to traverse the midgut wall. They transform into oocysts below the basal lamina of the midgut epithelium (Beier, 1998). These oocysts produce sporozoites that invade the salivary gland, ready to infect another vertebrate host during the next blood meal. These developmental stages of the rodent malaria Plasmodium yoelii nigeriensis cause a significant reduction in the number of eggs produced by Anopheles stephensi and Anopheles gambiae following successive blood meals (Hogg and Hurd, 1995a; Hogg and Hurd, 1995b; Ahmed et al., 1999). Thus, the impact of infection upon mosquito reproductive fitness is cumulative. Mosquito meroistic ovaries contain a series of approximately 50 ovarioles that radiate from a calyx. Each ovariole consists of a germarium and two follicles or egg chambers. The latter are composed of one oocyte and seven nurse cells and are enclosed in a follicular epithelium (Sokolova, 1994). Egg production is cyclical and synchronous. A blood meal initiates the maturation of the proximate follicles, resulting in oviposition of an egg batch at the end of a gonotrophic cycle. During this process, the follicular epithelial cells become patent and separate to allow passage of 2773