Molecular and functional aspects of parasite invasion

Soldati, Dominique; Foth, Bernardo J.; Cowman, Alan F.

doi:10.1016/j.pt.2004.09.009

Cited by 109 publications

(81 citation statements)

References 73 publications

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“…NaTC enhances the gliding motility of C. parvum sporozoites. Gliding motility is a prerequisite for the invasive stage of most Apicomplexa (18,20) and is associated with apical organelle discharge of C. parvum (6). We next investigated whether NaTC enhanced the gliding motility of C. parvum sporozoites.…”

Section: Resultsmentioning

confidence: 99%

“…Whether or not bile salts induce calcium signaling in C. parvum or other Apicomplexa remains to be determined. The apical organelle discharge of C. parvum sporozoites also affects the gliding motility (6), which is essential for the initial invasion stage of many Apicomplexa (18,20). The presence of NaTC or other bile salts during inoculation increased the protein secretion and gliding motility of sporozoites, which presumably enhanced the rate of cell invasion.…”

Section: Discussionmentioning

confidence: 99%

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Bile Acids Enhance Invasiveness of Cryptosporidium spp. into Cultured Cells

et al. 2006

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Bile salts such as sodium taurocholate (NaTC) are routinely used to induce the excystation of Cryptosporidium oocysts. Here we show that NaTC significantly enhanced the invasion of several cultured cell lines by freshly excysted Cryptosporidium parvum and Cryptosporidium hominis sporozoites. A variety of purified bile salts or total bile from bovine also enhanced the invasion of cultured cells by C. parvum. Further studies demonstrated that NaTC increased protein secretion and gliding motility of sporozoites, the key processes for successful invasion. These observations may lead to improved Cryptosporidium infectivity of cultured cells and help future studies on the host-parasite interaction.As members of the phylum Apicomplexa, the enteric protozoa Cryptosporidium species share a common apical secreting apparatus that mediates locomotion during cellular invasion (5, 21). Cryptosporidium hominis and Cryptosporidium parvum, whose genomes were sequenced recently (1, 28), are the species most frequently linked with human cryptosporidiosis (21,27). Infection begins with the oral uptake of Cryptosporidium oocysts, the environmentally resistant form, which then pass through the acidic stomach before entering the small intestine, where they presumably excyst. Although the molecular and biochemical mechanisms involved in excystation are poorly understood, it is believed that host environmental factors, such as temperature, pH, proteases, bile salts, and possibly other unknown factors, trigger the excystation of ingested oocysts (19). The newly excysted sporozoites secrete adhesive molecules and other signaling proteins which have been demonstrated to play a key role in the initial attachment and cellular invasion (4, 6).The in vitro cell culture system, while limited to the asexual phase, has been a useful tool for investigating early parasite attachment and invasion and has been applied to measure Cryptosporidium infectivity and for screening of compounds for inhibitory activity (3,17). Several cell lines, including human ileocecal adenocarcinoma (HCT-8), human colonic adenocarcinoma (Caco-2), and Madin-Darby bovine kidney (MDBK) cell lines, are widely used for Cryptosporidium in vitro studies (12,22). To initiate in vitro infection, purified Cryptosporidium oocysts are often treated with sodium hypochlorite either alone or followed by sodium taurocholate (NaTC)-trypsin treatment before infecting cell monolayers. Several publications have dealt with assessment of the conditions and materials for optimal oocyst excystation and tissue culture infection by the excysted sporozoites (15,16,23,24). Upton et al. (24) investigated the optimization of infection of oocysts treated with bleach without prior excystation. Gold et al. showed that the presence of NaTC in the culture medium enhanced infection when oocysts were directly added to cell culture monolayers (11). However, the nature of this enhancement was not fully investigated, and it was assumed that the NaTC facilitated the excystation of oocysts in the culture medium (...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bile Acids Enhance Invasiveness of Cryptosporidium spp. into Cultured Cells

et al. 2006

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“…2A). Lack of complete co-localization between the components is not unexpected, since the intact motor complex is predicted to form only transiently at the moving junction (20,37). Close inspection of the reactivity with anti-PfMTIP ( Fig.…”

Section: Motor Complex Proteins Pfgap45 and Pfgap50 Are Expressed Inmentioning

confidence: 97%

A Conserved Molecular Motor Drives Cell Invasion and Gliding Motility across Malaria Life Cycle Stages and Other Apicomplexan Parasites

Baum

Richard

Healer

et al. 2006

Journal of Biological Chemistry

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341

405

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Apicomplexan parasites constitute one of the most significant groups of pathogens infecting humans and animals. The liver stage sporozoites of Plasmodium spp. and tachyzoites of Toxoplasma gondii, the causative agents of malaria and toxoplasmosis, respectively, use a unique mode of locomotion termed gliding motility to invade host cells and cross cell substrates. This amoeboid-like movement uses a parasite adhesin from the thrombospondin-related anonymous protein (TRAP) family and a set of proteins linking the extracellular adhesin, via an actin-myosin motor, to the inner membrane complex. The Plasmodium blood stage merozoite, however, does not exhibit gliding motility. Here we show that homologues of the key proteins that make up the motor complex, including the recently identified glideosome-associated proteins 45 and 50 (GAP40 and GAP50), are present in P. falciparum merozoites and appear to function in erythrocyte invasion. Furthermore, we identify a merozoite TRAP homologue, termed MTRAP, a micronemal protein that shares key features with TRAP, including a thrombospondin repeat domain, a putative rhomboid-protease cleavage site, and a cytoplasmic tail that, in vitro, binds the actinbinding protein aldolase. Analysis of other parasite genomes shows that the components of this motor complex are conserved across diverse Apicomplexan genera. Conservation of the motor complex suggests that a common molecular mechanism underlies all Apicomplexan motility, which, given its unique properties, highlights a number of novel targets for drug intervention to treat major diseases of humans and livestock.Parasites from the phylum Apicomplexa represent some of the most significant human and agricultural pathogens. Their ranks include Theileria parva and Theileria annulata, parasites that give rise to lymphoproliferative diseases of cattle, the opportunistic pathogens Toxoplasma gondii and Cryptosporidium parvum that can cause life-threatening, prolonged infection in immunocompromised patients, and the most lethal of the group, the genus Plasmodium, in particular Plasmodium falciparum, the cause of millions of human deaths and as many as 500 million infections annually (1).Apicomplexa are a monophyletic group of obligate intracellular parasites that invade a wide range of host cells but lack the classical means of motility such as a flagellum or cilia. Instead, they move by a unique form of actin-based locomotion called gliding motility (for recent reviews, see Refs. 2-4). Efficient motility and invasion requires the release of proteins from secretory organelles located at the apical prominence, the defining structure of the phylum. These organelles, the micronemes, rhoptries, and dense granules contain many of the key proteins needed for directional attachment, cell invasion, and establishment of the parasitophorous vacuole (PV) 5 within the host cell (5). Much of our understanding of gliding motility comes from studies with the liver stage parasite from Plasmodium spp., the sporozoite, or the morphologically similar tac...

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“…Organisms that exploit this lifestyle are found among all major groups of pathogens, including viruses, bacteria, protozoa, fungi and helminthes (Andrade & Andrews, 2005, Despommier, 1998, Mendes-Giannini et al, 2005, Pizarro-Cerda & Cossart, 2006, Sibley, 2004, Sieczkarski & Whittaker, 2005. To gain access to intracellular resources obligate intracellular pathogens cross their host cell's plasma membrane using a variety of pathogenspecific mechanisms (Andrade & Andrews, 2005, Carruthers & Boothroyd, 2007, PizarroCerda & Cossart, 2006, Sieczkarski & Whittaker, 2005, Sieczkarski & Whittaker, 2005, Soldati et al, 2004.…”

Section: Introductionmentioning

confidence: 99%

Kinetic modeling of Toxoplasma gondii invasion

Kafsack

Carruthers

Pineda

2007

Journal of Theoretical Biology

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The phylum Apicomplexa includes parasites responsible for global scourges such as malaria, cryptosporidiosis, and toxoplasmosis. Parasites in this phylum reproduce inside the cells of their hosts, making invasion of host cells an essential step of their life cycle. Characterizing the stages of host-cell invasion, has traditionally involved tedious microscopic observations of individual parasites over time. As an alternative, we introduce the use of compartment models for interpreting data collected from snapshots of synchronized populations of invading parasites. Parameters of the model are estimated via a maximum negative log-likelihood principle. Estimated parameter values and their 95% confidence intervals (95% CI), are consistent with reported observations of individual parasites. For RH-strain parasites, our model yields that: 1) penetration of the host cell plasma membrane takes 26 sec (95% CI: 22-30 sec), 2) parasites that ultimately invade, remained attached 3 times longer than parasites that eventually detach from the host cells, and 3) 25% (95% CI: 19-33%) of parasites invade while 75% (95% CI: 67-81%) eventually detach from their host cells without progressing to invasion. A key feature of the model is the incorporation of invastion stages that cannot be directly observed. This allows us to characterize the phenomenon, of parasite detachment from host cells. The properties of this phenomenon would be difficult to quantify without a mathematical model. We conclude that mathematical modeling provides a powerful new tool for characterizing the stages of host-cell invasion by intracellular parasites.

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Molecular and functional aspects of parasite invasion

Cited by 109 publications

References 73 publications

Bile Acids Enhance Invasiveness of Cryptosporidium spp. into Cultured Cells

Bile Acids Enhance Invasiveness of Cryptosporidium spp. into Cultured Cells

A Conserved Molecular Motor Drives Cell Invasion and Gliding Motility across Malaria Life Cycle Stages and Other Apicomplexan Parasites

Kinetic modeling of Toxoplasma gondii invasion

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