title: Proteomic and systems biology analysis of the monocyte response to Coxiella burnetii infection.
abstract: Coxiella burnetii is an obligate intracellular bacterial pathogen and the causative agent of Q fever. Chronic Q fever can produce debilitating fatigue and C. burnetii is considered a significant bioterror threat. C. burnetii occupies the monocyte phagolysosome and although prior work has explained features of the host-pathogen interaction, many aspects are still poorly understood. We have conducted a proteomic investigation of human Monomac I cells infected with the Nine Mile Phase II strain of C. burnetii and used the results as a framework for a systems biology model of the host response. Our principal methodology was multiplex differential 2D gel electrophoresis using ZDyes, a new generation of covalently linked fluorescent protein detection dyes under development at Montana State University. The 2D gel analysis facilitated the detection of changes in posttranslational modifications on intact proteins in response to infection. The systems model created from our data a framework for the design of experiments to seek a deeper understanding of the host-pathogen interactions.
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Matt
authors.initials: M
authors.lastname: Shipman
authors.forename: Kirk
authors.initials: K
authors.lastname: Lubick
authors.forename: David
authors.initials: D
authors.lastname: Fouchard
authors.forename: Rajani
authors.initials: R
authors.lastname: Gurram
authors.forename: Paul
authors.initials: P
authors.lastname: Grieco
authors.forename: Mark
authors.initials: M
authors.lastname: Jutila
authors.forename: Edward A
authors.initials: EA
authors.lastname: Dratz
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D040501:Calgranulin A / Q000378:metabolism; D018834:Chaperonin 60 / Q000378:metabolism; D019295:Computational Biology; D016997:Coxiella burnetii; D016207:Cytokines / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D006801:Humans; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D013058:Mass Spectrometry; D024101:Mitochondrial Proteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D011755:Pyrophosphatases / Q000378:metabolism; D011778:Q Fever / Q000276:immunology*; D013482:Superoxide Dismutase / Q000378:metabolism; D049490:Systems Biology; D013997:Time Factors; D014153:Transaldolase / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D040501:Calgranulin A; D018834:Chaperonin 60; D016207:Cytokines; C060293:HSPD1 protein, human; D024101:Mitochondrial Proteins; D014746:Vimentin; D000090802:rab7 GTP-Binding Proteins; D013482:Superoxide Dismutase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D014153:Transaldolase; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D007931:Leucyl Aminopeptidase; D011755:Pyrophosphatases; D020691:rab GTP-Binding Proteins; D004746:Enoyl-CoA Hydratase