| Kinetic modeling of Toxoplasma gondii invasion. | |
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MedLine Citation:
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PMID: 17942124 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 26s (95% CI: 22-30s); (2) parasites that ultimately invade, remain attached three 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 invasion 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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Authors:
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Björn F C Kafsack; Vern B Carruthers; Fernando J Pineda |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-09-14 |
Journal Detail:
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Title: Journal of theoretical biology Volume: 249 ISSN: 0022-5193 ISO Abbreviation: J. Theor. Biol. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-11-26 Completed Date: 2008-03-19 Revised Date: 2013-03-27 |
Medline Journal Info:
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Nlm Unique ID: 0376342 Medline TA: J Theor Biol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 817-25 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Sciences Bldg. II, 1150 West Medical Center Dr., Ann Arbor, MI 48109-0620, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Host-Parasite Interactions Humans Models, Biological* Toxoplasma / pathogenicity*, physiology Toxoplasmosis / parasitology* Virulence / physiology |
| Grant Support | |
ID/Acronym/Agency:
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AI46675/AI/NIAID NIH HHS; R01 AI046675-01A1/AI/NIAID NIH HHS |
| Comments/Corrections | |
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