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dc.contributor.authorKhan, Mohd M.
dc.date.accessioned2019-05-02T19:10:24Z
dc.date.available2019-05-02T19:10:24Z
dc.identifier.urihttp://hdl.handle.net/10713/8972
dc.description2018
dc.descriptionToxicology
dc.descriptionUniversity of Maryland, Baltimore
dc.descriptionPh.D.
dc.description.abstractThe innate immune system is the first line of defense against pathogens. Pattern recognition receptors (PRRs), such as the Toll-like receptors (TLRs) sense and sample pathogen-associated molecular patterns (PAMPs). On the host myeloid cell surface, the proinflammatory Gram-negative bacterial outer membrane component lipopolysaccharide (LPS, also known as endotoxin) activates the innate immune system via TLR4. Intracellularly, LPS is detected by the noncanonical inflammasome through caspase4/5/11. In the present work, mass spectrometry (MS)-based top-down structural analysis of LPS uncovered major determinants of molecular pathogenesis, and MS-based systems immunoproteomics elucidated specific features of the immune response against endotoxin. We used targeted proteomics to profile the host response to the pathogens Escherichia coli, Staphylococcus aureus, and Burkholderia cenocepacia, and we discovered significant temporal changes in the macrophage secretome. Additionally, we identified global changes in protein secretion in TLR4- and caspase11- stimulated macrophages. Finally, we observed bacterial proteomic rewiring within the biofilm forms of Burkholderia, possibly explaining the observed lowering in sensitivity to antibiotics.
dc.subjectsecretomicsen_US
dc.subjectsystems immunoproteomicsen_US
dc.subject.meshEndotoxinsen_US
dc.subject.meshGram-Negative Bacteriaen_US
dc.subject.meshHost-Pathogen Interactionsen_US
dc.subject.meshProteomicsen_US
dc.titleMass Spectrometry based structural analysis and systems immunoproteomics strategies deduce specifics of host-pathogen interactions
dc.typedissertationen_US
dc.date.updated2019-04-30T11:36:16Z
dc.language.rfc3066en
dc.contributor.advisorGoodlett, David Robinson, 1960-
dc.description.embargo07/01/2019
refterms.dateFOA2019-05-02T19:10:24Z


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