Kinetic modeling of Toxoplasma gondii invasion

Kafsack, Björn F.C.; Carruthers, Vern B.; Pineda, Fernando

doi:10.1016/j.jtbi.2007.09.008

Cited by 22 publications

(19 citation statements)

References 28 publications

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“…6B). Numbers of intimately attached parasites remaining after 2 min increased at the 60-min time point, which is consistent with the finding that only a certain percentage of contact stage parasites will rapidly release their micronemes, while others will take longer to become intimately attached (17). Taken together with the finding that nocodazole reduced early but not late invasion, these data demonstrate that nocodazole has no detectable impact on parasite contact or intimate attachment.…”

Section: Disruption Of the Host Microtubule Cytoskeleton Transiently supporting

confidence: 85%

“…Assays to measure parasite contact with and intimate attachment to host cells were performed essentially as previously described but with minor modifications (17). Briefly, GFP ϩ parasites were added to confluent HFF monolayers (MOI of 10:1) in high-potassium buffer and then incubated for 20 min at 37°C to allow parasites to settle onto the monolayer.…”

Section: Methodsmentioning

confidence: 99%

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Host Cell Invasion by Toxoplasma gondii Is Temporally Regulated by the Host Microtubule Cytoskeleton

et al. 2010

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Toxoplasma gondii is an obligate intracellular protozoan parasite that invades and replicates within most nucleated cells of warm-blooded animals. The basis for this wide host cell tropism is unknown but could be because parasites invade host cells using distinct pathways and/or repertoires of host factors. Using synchronized parasite invasion assays, we found that host microtubule disruption significantly reduces parasite invasion into host cells early after stimulating parasite invasion but not at later time points. Host microtubules are specifically associated with the moving junction, which is the site of contact between the host cell and the invading parasite. Host microtubules are specifically associated with the moving junction of those parasites invading early after stimulating invasion but not with those invading later. Disruption of host microtubules has no effect on parasite contact, attachment, motility, or rate of penetration. Rather, host microtubules hasten the time before parasites commence invasion. This effect on parasite invasion is distinct from the role that host microtubules play in bacterial and viral infections, where they function to traffic the pathogen or pathogenderived material from the host cell's periphery to its interior. These data indicate that the host microtubule cytoskeleton is a structure used by Toxoplasma to rapidly infect its host cell and highlight a novel function for host microtubules in microbial pathogenesis.Toxoplasma gondii is an obligate intracellular protozoan parasite that is capable of causing disease in fetuses and immunocompromised individuals (23). The parasite infects a wide range of nucleated cells of most warm-blooded animals. The mechanisms underlying this wide tropism are not known but could be due to either the parasite infecting cells using a ubiquitously expressed host receptor and associated machinery, inserting its own receptor into the host cell's plasma membrane, or using multiple host cell receptors/machinery (5).Toxoplasma invasion is a multistep, complex process consisting of parasite contact to host cells, intimate attachment, parasite motility, and then penetration (5). Host cell contact is a loose, low-affinity interaction that is mediated by parasite surface antigens. An unknown signal then triggers the release of proteins from a specialized secretory organelle called micronemes whose contents include proteins that function as adhesins. This is then followed by parasite gliding motility on the host cell surface. At some point, proteins from a second secretory organelle, named rhoptries, are exocytosed. Among these rhoptry proteins, several (RON2, RON4, RON5, and RON8) are part of a preformed complex that binds the previously secreted AMA1 microneme protein (1,2,20,33). Together, these proteins form the moving junction complex, which defines the parasite entry site on the host cell plasma membrane. Parasite penetration occurs by the parasite propel-

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Section: Disruption Of the Host Microtubule Cytoskeleton Transiently supporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Host Cell Invasion by Toxoplasma gondii Is Temporally Regulated by the Host Microtubule Cytoskeleton

et al. 2010

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“…Upon reaching a confluence of 30 to 50%, cell cultures were synchronized by serum deprivation (0.5% FBS) for 2 days. Parasites were released from intracellular vacuoles by syringe lysis, filter purified (13), and then resuspended in Endo buffer (44.7 mM K 2 SO 4 , 10 mM MgSO 4 , 106 mM sucrose, 5 mM glucose, 20 mM Tris-H 2 SO 4 , 3.5 mg/ml BSA, pH 8.2), a potassium buffer used in the synchronization of tachyzoite invasion (27). Briefly, at the time of infection, the synchronized cells were inoculated with tachyzoites at a multiplicity of infection (MOI) of 3 or with Endo buffer alone (mock-infected controls).…”

Section: Methodsmentioning

confidence: 99%

Differential Effects of Three CanonicalToxoplasmaStrains on Gene Expression in Human Neuroepithelial Cells

Xiao¹,

Jones‐Brando²,

Talbot³

et al. 2011

Infect Immun

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Strain type is one of the key factors suspected to play a role in determining the outcome of Toxoplasma infection. In this study, we examined the transcriptional profile of human neuroepithelioma cells in response to representative strains of Toxoplasma by using microarray analysis to characterize the strain-specific host cell response. The study of neural cells is of interest in light of the ability of Toxoplasma to infect the brain and to establish persistent infection within the central nervous system. We found that the extents of the expression changes varied considerably among the three strains. Neuroepithelial cells infected with Toxoplasma type I exhibited the highest level of differential gene expression, whereas type II-infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to the central nervous system, while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter the expression of a clearly defined set of genes. Moreover, Ingenuity Pathways Analysis (IPA) suggests that the three lineages differ in the ability to manipulate their host; e.g., they employ different strategies to avoid, deflect, or subvert host defense mechanisms. These observed differences may explain some of the variation in the neurobiological effects of different strains of Toxoplasma on infected individuals.

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“…This is mediated by the secreted microneme proteins and subsequently by the formation of the moving junction (MJ) (74). The MJ is a cooperative structure between the microneme protein AMA1 and proteins residing in the rhoptry neck (RON proteins).…”

Section: Host Cell Egress and Invasionmentioning

confidence: 99%

Lytic Cycle of Toxoplasma gondii: 15 Years Later

Blader

Coleman

Chen

et al. 2015

Annu. Rev. Microbiol.

236

189

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Toxoplasmosis is the clinical and pathological consequence of acute infection with the obligate intracellular apicomplexan parasite Toxoplasma gondii. Symptoms result from tissue destruction that accompanies lytic parasite growth. This review updates current understanding of the host cell invasion, parasite replication and eventual egress that comprise the lytic cycle, as well as the ways T. gondii manipulates host cells to assure survival. Since the publication of a previous iteration of this review 15 years ago, important advances have been made in our molecular understanding of parasite growth and mechanisms of host cell egress, and knowledge of the parasite’s manipulation of the host has rapidly progressed. Here we cover molecular advances and current conceptual frameworks that include each of these topics, with an eye to what might be known 15 years from now.

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Kinetic modeling of Toxoplasma gondii invasion

Cited by 22 publications

References 28 publications

Host Cell Invasion by Toxoplasma gondii Is Temporally Regulated by the Host Microtubule Cytoskeleton

Host Cell Invasion by Toxoplasma gondii Is Temporally Regulated by the Host Microtubule Cytoskeleton

Differential Effects of Three CanonicalToxoplasmaStrains on Gene Expression in Human Neuroepithelial Cells

Lytic Cycle of Toxoplasma gondii: 15 Years Later

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