Host–pathogen interactions: a proteomic view

Zhang, Celia G.; Chromy, Brett A.; McCutchen-Maloney, Sandra L.

doi:10.1586/14789450.2.2.187

Cited by 51 publications

(28 citation statements)

References 88 publications

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“…Only a few comparative proteomic analyses of the host response to infection have been published to date, and these have focused on bacterial and viral pathogens (43,97). A key question that arises from this study that demonstrates such an active and apparently specific response from the cell is to what degree the response is shared with all intracellular pathogens and which processes are specific to T. gondii (or Apicomplexa in general).…”

Section: Vol 76 2008 Modulation Of the Host Cell Proteome By T Gonmentioning

confidence: 97%

Modulation of the Host Cell Proteome by the Intracellular Apicomplexan ParasiteToxoplasma gondii

et al. 2008

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To investigate how intracellular parasites manipulate their host cell environment at the molecular level, we undertook 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, while 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 mitochondrion-enriched preparation from infected cells. Comparison of our proteomic data with previous transcriptional studies suggested that a complex relationship exits between transcription and protein expression that may be partly explained by posttranslational modifications of proteins and revealed 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, in terms of both protein expression changes and protein modifications, and reveal a complex and intimate molecular relationship between host and parasite.The obligate intracellular protozoan Toxoplasma gondii has evolved an intimate relationship with its host that extends to the cellular and molecular levels (82, 83). The absolute requirement for invasion of an appropriate host cell in the replication of the parasite suggests that modification of host functions is central to pathogenesis. Intuitively, this subversion of the cell must be a complex process, since host cells are not inherently programmed to provide an environment conducive to pathogens. Host cells have evolved primary lines of defense as countermeasures to pathogen invasion, establishment, and replication. These include elaborate systems, such as the phagolysosomal fusion, reactive oxygen and nitrogen intermediates, the sequestration of nutrients, and even cell suicide (apoptosis), as defenses to limit pathogen growth. The implementation of these systems and the ability of successful pathogens to mitigate their effects are ultimately mediated by changes in both the levels and activities of key proteins. While some of these changes may be transcriptionally regulated and thus potentially revealed by microarray analysis, the true effectors are proteins,...

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Section: Vol 76 2008 Modulation Of the Host Cell Proteome By T Gonmentioning

confidence: 97%

Modulation of the Host Cell Proteome by the Intracellular Apicomplexan ParasiteToxoplasma gondii

et al. 2008

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“…Basing on this, comparative proteome analyses are often used to generate more detailed understanding of molecular mechanisms behind diseases [7]. In fact, in vivo models combined with proteomic technological advances represent unprecedented means of characterizing host-pathogen interactions [8]. This approach enables a systematic identification and classification of host proteins involved in infection, providing new targets for disease prevention and treatment strategies [9].…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of porcine mesenteric lymph-nodes after Salmonella typhimurium infection

Martins¹,

Collado-Romero²,

Martínez-Gomáriz³

et al. 2012

Journal of Proteomics

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“…Potential biomarkers for disease detection from proteomic methodologies have been widely used. Atherosclerosis, diabetes mellitus, cardiovascular, neuronal, ocular, liver, renal and infectious diseases are only a few examples that can illustrate the efforts that are being made, in recent years, in the discovery of new biomarkers [73][74][75][76][77][78][79][80][81][82][83][84][85][86][87].…”

Section: Proteomics In Biomarker Discoverymentioning

confidence: 99%

A better understanding of molecular mechanisms underlying human disease

Bermúdez-Crespo

López

2007

Proteomics Clinical Apps

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This review summarises and discusses the degree to which proteomics is contributing to medical care, providing examples and signspots for future directions. Why do genomic approaches provide a limited view of gene expression? Because of the multifactorial nature of many diseases, proteomics enables us to understand the molecular basis of disease, not only at the organism, whole‐cell or tissue levels, but also in subcellular structures, protein complexes and biological fluids. The application of proteomics in medicine is expected to have a major impact by providing an integrated view of individual disease processes. This review describes several proteomic platforms and examines the role of proteomics as a tool for clinical biomarker discovery, the identification of prognostic and earlier diagnostic markers, their use in monitoring the effects of drug treatments and eventually find more efficient and safer therapeutics for a wide range of pathologies.

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Host–pathogen interactions: a proteomic view

Cited by 51 publications

References 88 publications

Modulation of the Host Cell Proteome by the Intracellular Apicomplexan ParasiteToxoplasma gondii

Modulation of the Host Cell Proteome by the Intracellular Apicomplexan ParasiteToxoplasma gondii

Proteomic analysis of porcine mesenteric lymph-nodes after Salmonella typhimurium infection

A better understanding of molecular mechanisms underlying human disease

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