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181.
Na+/H+ exchangers (NHEs) are ubiquitous membrane proteins that catalyze the exchange of Na+ for H+ and are critical in pH and cell volume regulation, as well as osmotolerance. In this study, we identify and characterize a novel NHE, TgNHE2, in Toxoplasma gondii. Immunofluorescence studies show that TgNHE2 is localized to the rhoptries, secretory organelles involved in invasion. TgNHE2 is the first intracellular NHE to be characterized in a protozoan parasite and its localization suggests possible roles for the rhoptries in osmotolerance and/or as secretory lysosomes-like granules. 相似文献
182.
Identification of the moving junction complex of Toxoplasma gondii: a collaboration between distinct secretory organelles 总被引:1,自引:0,他引:1
Apicomplexan parasites, including Toxoplasma gondii and Plasmodium sp., are obligate intracellular protozoa. They enter into a host cell by attaching to and then creating an invagination in the host cell plasma membrane. Contact between parasite and host plasma membranes occurs in the form of a ring-shaped moving junction that begins at the anterior end of the parasite and then migrates posteriorly. The resulting invagination of host plasma membrane creates a parasitophorous vacuole that completely envelops the now intracellular parasite. At the start of this process, apical membrane antigen 1 (AMA1) is released onto the parasite surface from specialized secretory organelles called micronemes. The T. gondii version of this protein, TgAMA1, has been shown to be essential for invasion but its exact role has not previously been determined. We identify here a trio of proteins that associate with TgAMA1, at least one of which associates with TgAMA1 at the moving junction. Surprisingly, these new proteins derive not from micronemes, but from the anterior secretory organelles known as rhoptries and specifically, for at least two, from the neck portion of these club-shaped structures. Homologues for these AMA1-associated proteins are found throughout the Apicomplexa strongly suggesting that this moving junction apparatus is a conserved feature of this important class of parasites. Differences between the contributing proteins in different species may, in part, be the result of selective pressure from the different niches occupied by these parasites. 相似文献
183.
Extracellular Toxoplasma parasites are sensitive to pyrrolidine dithiocarbamate (PDTC) at low micromolar concentrations. Loss of parasite viability following PDTC treatment is shown to be mediated by oxidation, which is reminiscent of PDTC killing in mammalian cells. Intracellular parasites, by contrast, are resistant to PDTC killing, although treatment does cause reversible growth arrest. In addition to the possible implications relative to the biology of the parasite, these observations suggest that PDTC could be of use in eliminating undesired extracellular parasites during assays and selections in vitro. 相似文献
184.
Lytic cycle of Toxoplasma gondii. 总被引:2,自引:0,他引:2
Toxoplasma gondii is an obligate intracellular pathogen within the phylum Apicomplexa. This protozoan parasite is one of the most widespread, with a broad host range including many birds and mammals and a geographic range that is nearly worldwide. While infection of healthy adults is usually relatively mild, serious disease can result in utero or when the host is immunocompromised. This sophisticated eukaryote has many specialized features that make it well suited to its intracellular lifestyle. In this review, we describe the current knowledge of how the asexual tachyzoite stage of Toxoplasma attaches to, invades, replicates in, and exits the host cell. Since this process is closely analogous to the way in which viruses reproduce, we refer to it as the Toxoplasma "lytic cycle." 相似文献
185.
186.
A Toxoplasma gondii locus required for the direct manipulation of host mitochondria has maintained multiple ancestral functions
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Matthew L. Blank Michelle L. Parker Raghavendran Ramaswamy Cameron J. Powell Elizabeth D. English Yaw Adomako‐Ankomah Lena F. Pernas Sean D. Workman John C. Boothroyd Martin J. Boulanger Jon P. Boyle 《Molecular microbiology》2018,108(5):519-535
The Toxoplasma gondii locus mitochondrial association factor 1 (MAF1) encodes multiple paralogs, some of which mediate host mitochondrial association (HMA). Previous work showed that HMA was a trait that arose in T. gondii through neofunctionalization of an ancestral MAF1 ortholog. Structural analysis of HMA‐competent and incompetent MAF1 paralogs (MAF1b and MAF1a, respectively) revealed that both paralogs harbor an ADP ribose binding macro‐domain, with comparatively low (micromolar) affinity for ADP ribose. Replacing the 16 C‐terminal residues of MAF1b with those of MAF1a abrogated HMA, and we also show that only three residues in the C‐terminal helix are required for MAF1‐mediated HMA. Importantly these same three residues are also required for the in vivo growth advantage conferred by MAF1b, providing a definitive link between in vivo proliferation and manipulation of host mitochondria. Co‐immunoprecipitation assays reveal that the ability to interact with the mitochondrial MICOS complex is shared by HMA‐competent and incompetent MAF1 paralogs and mutants. The weak ADPr coordination and ability to interact with the MICOS complex shared between divergent paralogs may represent modular ancestral functions for this tandemly expanded and diversified T. gondii locus. 相似文献
187.
188.
Kevin A. Brown Laurie J. Lambert James M. Brophy James Nasmith Stéphane Rinfret Eli Segal Simon Kouz Dave Ross Richard Harvey Sébastien Maire Lucy J. Boothroyd Peter Bogaty 《PloS one》2014,9(8)
Background
Many patients with ST-elevation myocardial infarction (STEMI) do not receive reperfusion therapy and are known to have poorer outcomes. We aimed to perform the first population-level, integrated analysis of clinical, ECG and hospital characteristics associated with non-receipt of reperfusion therapy in patients with STEMI.Methods and Results
This systematic evaluation of STEMI care in 82 hospitals in Quebec included all patients with a discharge diagnosis of myocardial infarction, presenting with characteristic symptoms and an ECG showing STEMI as attested by at least one of two study cardiologists or left bundle branch block (LBBB). Excluding LBBB, an ECG was considered a definite STEMI diagnosis if both cardiologists scored ‘certain STEMI’ and ambiguous if one scored ‘uncertain’ or ‘not STEMI’. Centers were classified according to accessibility to primary percutaneous coronary intervention (PPCI): 1) on-site PPCI; 2) routine transfer for PPCI; 3) varying mix of PPCI transfer and on-site fibrinolysis; and 4) routine on-site fibrinolysis. Of 3730 STEMI/LBBB patients, 812 (21.8%) did not receive reperfusion therapy. In multivariate analysis, likelihood of no reperfusion therapy was a function of PPCI accessibility (odds ratio [OR] for fibrinolysis versus PPCI centers = 3.1; 95% CI: 2.2–4.4), presence of LBBB (OR = 24.1; 95% CI: 17.8–32.9) and an ECG ambiguous for STEMI (OR = 4.1; 95% CI: 3.3–5.1). When the ECG was ambiguous, likelihood of no reperfusion therapy was highest in hospitals most distant from PPCI centers.Conclusions
ECG diagnostic ambiguity, LBBB and PPCI accessibility are important predictors of not receiving reperfusion therapy, suggesting opportunities for improving outcomes. 相似文献189.
Aliaksandr Khaminets Julia P. Hunn Stephanie Könen‐Waisman Yang O. Zhao Daniela Preukschat Jörn Coers Jon P. Boyle Yi‐Ching Ong John C. Boothroyd Gabriela Reichmann Jonathan C. Howard 《Cellular microbiology》2010,12(7):939-961
The immunity‐related GTPases (IRGs) constitute an interferon‐induced intracellular resistance mechanism in mice against Toxoplasma gondii. IRG proteins accumulate on the parasitophorous vacuole membrane (PVM), leading to its disruption and to death of the parasite. How IRGs target the PVM is unknown. We show that accumulation of IRGs on the PVM begins minutes after parasite invasion and increases for about 1 h. Targeting occurs independently of several signalling pathways and the microtubule network, suggesting that IRG transport is diffusion‐driven. The intensity of IRG accumulation on the PVM, however, is reduced in absence of the autophagy regulator, Atg5. In wild‐type cells IRG proteins accumulate cooperatively on PVMs in a definite order reflecting a temporal hierarchy, with Irgb6 and Irgb10 apparently acting as pioneers. Loading of IRG proteins onto the vacuoles of virulent Toxoplasma strains is attenuated and the two pioneer IRGs are the most affected. The polymorphic rhoptry kinases, ROP16, ROP18 and the catalytically inactive proteins, ROP5A–D, are not individually responsible for this effect. Thus IRG proteins protect mice against avirulent strains of Toxoplasma but fail against virulent strains. The complex cooperative behaviour of IRG proteins in resisting Toxoplasma may hint at undiscovered complexity also in virulence mechanisms. 相似文献
190.