Transmembrane insertion of the Toxoplasma gondii GRA5 protein occurs after soluble secretion into the host cell.
(9/3339)
The intracellular parasite Toxoplasma gondii resides within a specialized compartment, the parasitophorous vacuole (PV), that resists fusion with host cell endocytic and lysosomal compartments. The PV is extensively modified by secretion of parasite proteins, including the dense granule protein GRA5 that is specifically targeted to the delimiting membrane of the PV (PVM). We show here that GRA5 is present both in a soluble form and in hydrophobic aggregates. GRA5 is secreted as a soluble form into the PV after which it becomes stably associated with the PVM. Topological studies demonstrated that GRA5 was inserted into the PVM as a transmembrane protein with its N-terminal domain extending into the cytoplasm and its C terminus in the vacuole lumen. Deletion of 8 of the 18 hydrophobic amino acids of the single predicted transmembrane domain resulted in the failure of GRA5 to associate with the PVM; yet it remained correctly packaged in the dense granules and was secreted as a soluble protein into the PV. Collectively, these studies demonstrate that the secretory pathway in Toxoplasma is unusual in two regards; it allows soluble export of proteins containing typical transmembrane domains and provides a mechanism for their insertion into a host cell membrane after secretion from the parasite. (+info)
Host haematological factors influencing the transmission of Plasmodium falciparum gametocytes to Anopheles gambiae s.s. mosquitoes.
(10/3339)
We investigated the relationship between selected host haematological and parasitological parameters and the density and infectivity of Plasmodium falciparum gametocytes. 143 individuals (age range 1-62 years) attending an outpatient clinic in Farafenni, The Gambia, who had peripheral blood gametocytaemia were recruited (mean gametocyte density 123.7/microl, range 5-17,000/microl). Of the parameters measured, packed cell volume (PCV), reticulocyte count (RetC) and lymphocyte count (LyC) were significantly associated with gametocyte density (r = - 0.17, P < 0.05; r = 0.21, P < 0.01; r = 0.18, P < 0.05, respectively). Data from membrane feeding experiments in which 15 or more mosquitoes were dissected showed that 60.7% (53/87) of gametocyte carriers infected one or more mosquitoes. Gametocyte density was strongly correlated with transmission success (TS) (r = 0.3, P < 0.005) and, in successful infections, with both mosquito prevalence (MP) (r = 0.36, P < 0.005) and mean oocyst burden (MOB) (r = 0.65, P < 0.0001). None of the other factors measured were significantly associated with any of these indices in bivariate analysis. Regression modelling showed that both gametocyte density and PCV were positively associated with gametocyte carrier infectivity to mosquitoes (LRchi2 = 100.7 and 47.2, respectively) and, in successful infections, with MOB (beta = 0.16, t = 4.9, P < 0.001; beta = 0.02, t = 2.3, P < 0.05, respectively). The positive association with PCV suggests that blood meal quality influences infection probably as a nutritional requirement, however, as this effect was most apparent at high gametocyte densities, its epidemiological significance is questionable. Though the haematological parameters associated with gametocyte density are a direct consequence of asexual infection, they may also represent an adaptive mechanism for optimization of sexual stage development. (+info)
Horizontal transfer of Wolbachia between phylogenetically distant insect species by a naturally occurring mechanism.
(11/3339)
Wolbachia is a genus of alpha-proteobacteria found in obligate intracellular association with a wide variety of arthropods, including an estimated 10-20% of all insect species [1]. Wolbachia represents one of a number of recently identified 'reproductive parasites' [2] which manipulate the reproduction of their hosts in ways that enhance their own transmission [3] [4] [5] [6] [7] [8] [9]. The influence of Wolbachia infection on the dynamics of host populations has focused considerable interest on its possible role in speciation through reproductive isolation [3] [10] [11] and as an agent of biological control [2] [12] [13]. Although Wolbachia normally undergoes vertical transmission through the maternal line of its host population [14], there is compelling evidence from molecular phylogenies that extensive horizontal (intertaxon) transmission must have occurred [1] [9] [15] [16] [17]. Some of the best candidate vectors for the horizontal transmission of Wolbachia are insect parasitoids [15], which comprise around 25% of all insect species and attack arthropods from an enormous range of taxa [18]. In this study, we used both fluorescence microscopy and PCR amplification with Wolbachia-specific primers to show that Wolbachia can be transmitted to a parasitic wasp (Leptopilina boulardi) from its infected host (Drosophila simulans) and subsequently undergo diminishing vertical transmission in this novel host species. These results are, to our knowledge, the first to reveal a natural horizontal transfer route for Wolbachia between phylogenetically distant insect species. (+info)
Molecular mechanisms of cytoadherence in malaria.
(12/3339)
Microbial pathogens subvert host adhesion molecules to disseminate or to enter host cells to promote their own survival. One such subversion is the cytoadherence of Plasmodium falciparum-infected erythrocytes (IRBC) to vascular endothelium, which protects the parasite from being removed by the spleen. The process results in microcirculatory obstruction and subsequent hypoxia, metabolic disturbances, and multiorgan failure, which are detrimental to the host. Understanding the molecular events involved in these adhesive interactions is therefore critical both in terms of pathogenesis and implications for therapeutic intervention. Under physiological flow conditions, cytoadherence occurs in a stepwise fashion through parasite ligands expressed on the surface of IRBC and the endothelial receptors CD36, intercellular adhesion molecule-1 (ICAM-1), P-selectin, and vascular adhesion molecule-1. Moreover, rolling on ICAM-1 and P-selectin increases subsequent adhesion to CD36, indicating that receptors can act synergistically. Cytoadherence may activate intracellular signaling pathways in both endothelial cells and IRBC, leading to gene expression of mediators such as cytokines, which could modify the outcome of the infection. (+info)
The effects of host heterogeneity on pathogen population structure.
(13/3339)
We have shown that among pathogens, populations may self-organize into strains with non-overlapping repertoires of antigenic variants as a consequence of strong immune selection operating on polymorphic antigens. Recently, we have also demonstrated that over a wide range of intermediate levels of immune selection, pathogens may still be structured into discrete strains, but different sets of non-overlapping pathogen types will replace each other in a cyclical or chaotic manner. These models assume that the ranking of antigens in terms of the strength of the induced immune response is the same for every host. However, host immune responses may be restricted by the genotype of the individual. To explore this issue, a mathematical model was constructed under the assumption that a proportion of the host population responds principally to a variable antigen while the remainder of the population responds principally to a conserved antigen. The results of this analysis indicate that discrete strain structure (DSS) will be maintained even with a high frequency of hosts that do not respond in a variant-specific manner. Furthermore, the range of the immune selection pressure over which DSS prevails is increased (and the region of cyclical or chaotic behaviour reduced) by the inclusion of hosts that respond in a cross-reactive rather than a variant-specific manner. (+info)
Infection status of dragonflies with Plagiorchis muris metacercariae in Korea.
(14/3339)
Plagiorchis muris has been found in both house and field rats as well as in humans. The infection status of the second intermediate hosts of P. muris is prerequisite in understanding their biological features in an ecosystem. Six species of dragonflies were caught in a wide range of areas in Korea; and they were Sympetrum darwinianum, S. eroticum, S. pedomontanum, S. infuscatum, Pantala flavoscens, Calopteryx atrata, and Orthetrum albistylum speciosum. The occurrence of P. muris metacercariae in dragonflies was nationwide with various infection rates. The metacercarial burden of P. muris in the surveyed areas was the highest in S. eroticum followed by S. darwinianum, S. pedomontanum, and C. atrata. The highest infection rate by P. muris metacercariae was found in S. darwinianum followed by S. eroticum. The metacercarial burden was particularly heavy in the dragonflies found in Hamyang-gun and Kosong-gun, Kyongsangnam-do. It is, therefore, likely that dragonflies play a significant role as the second intermediate host in the life cycle of P. muris in Korea. (+info)
Induction of histamine release in parasitized individuals by somatic and cuticular antigens from Onchocerca volvulus.
(15/3339)
The host immune response in onchocerciasis is believed to contribute to the clinical manifestations of infection. Mazzotti and chronic inflammatory reactions might be mediated by mechanisms involving specific IgE and reactivity of mast cells and basophils to the parasite antigens. In this report, we show that Onchocerca volvulus antigens are capable of inducing histamine release. Three types of extracts were prepared from the parasite: soluble total, surface, and cuticular collagen. Soluble extracts released histamine in all individuals with onchocerciasis at significantly higher levels (P < 0.05) than those found in endemic controls, but similar levels to those found in patients with mansonellosis. However, cuticular collagen induced significantly (P < 0.01) higher histamine release in patients with onchocerciasis than in those with mansonellosis. No reactivity against human type IV collagen was observed. Implications derived from the presence of sensitized basophils in the pathogenesis of onchocerciasis are discussed. (+info)
Rifins: a second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum.
(16/3339)
Many pathogens evade the host immune response or adapt to their environment by expressing surface proteins that undergo rapid switching. In the case of Plasmodium falciparum, products of a multigene family known as var are expressed on the surface of infected red cells, where they undergo clonal antigenic variation and contribute to malaria pathogenesis by mediating adhesion to a variety of host endothelial receptors and to uninfected red blood cells by forming rosettes. Herein we show that a second gene family, rif, which is associated with var at subtelomeric sites in the genome, encodes clonally variant proteins (rifins) that are expressed on the infected red cell surface. Their high copy number, sequence variability, and red cell surface location indicate an important role for rifins in malaria host-parasite interaction. (+info)