Wednesday, October 31, 2007

Modulation of the host cell proteome by Toxo

Infect Immun. 2007 Oct 29; [Epub ahead of print]

Modulation of the host cell proteome by the intracellular apicomplexan parasite Toxoplasma gondii

Nelson MM, Jones AR, Carmen JC, Sinai AP, Burchmore R, Wastling JM.

Department of Pre-Clinical Veterinary Science & Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Liverpool, L69 7ZJ. United Kingdom; Division of Infection and Immunity and Sir Henry Welcome Functional Genomics Facility, University of Glasgow, Glasgow, G12 8QQ. United Kingdom; School of Computer Science, University of Manchester, Manchester, M13 9PL. United Kingdom; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536, USA.

To investigate how intracellular parasites manipulate their host cell environment at the molecular level we have undertaken a quantitative proteomic study of cells following infection with the apicomplexan parasite Toxoplasma gondii. Using conventional two-dimensional electrophoresis, difference-gel electrophoresis (DIGE) and mass spectrometry, we identified host proteins that were consistently modulated in expression following infection. We detected modification of protein expression in key metabolic pathways including glycolysis, lipid and sterol metabolism, mitosis, apoptosis and structural protein expression, suggestive of global reprogramming of cell metabolism by the parasite. Many of the differentially expressed proteins had not been previously implicated in the response to the parasite, whilst others provide important corroborative protein evidence for previously proposed hypotheses of pathogen-cell interactions. Significantly, over one third of all modulated proteins were mitochondrial and this was further investigated by DIGE analysis of a mitochondrial-enriched preparation from infected cells. Comparison of our proteomic data with previous transcriptional studies suggested a complex relationship exits between transcription and protein expression that may be partly explained by post-translational modifications of proteins and reveals the importance of investigating protein changes when interpreting transcriptional data. To investigate this further we used phosphatase treatment and DIGE to demonstrate changes in the phosphorylation states of several key proteins following infection. Overall our findings indicate that the host cell proteome responds in a dramatic way to T. gondii invasion both in terms of protein expression changes and protein modifications and reveal a complex and intimate molecular relationship between host and parasite.

PMID: 17967855 [PubMed - as supplied by publisher]

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