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Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
Subcellular proteomic analysis of host-pathogen interactions using human monocytes exposed to Yersinia pestis and
Celia G Zhang1, Arlene D Gonzales, Megan W Choi
1Biodefense Division, Lawrence National Laboratory, Livermore, CA 94550, USA.
Abstract:
Yersinia pestis, the etiological agent of plague, is of concern to human health both from an infectious disease and a biodefense perspective. While Y. pestis and Yersinia pseudotuberculosis share more than 90% DNA homology, they have significantly different clinical manifestations. Plague is often fatal if untreated, yet Y. pseudotuberculosis causes severe intestinal distress but is rarely fatal. A better understanding of host response to these closely related pathogens may help explain the different mechanisms of virulence and pathogenesis that result in such different clinical outcomes. The aim of this study was to characterize host protein expression changes in human monocyte U937 cells after exposure to Y. pestis and Y. pseudotuberculosis. In order to gain global proteomic coverage of host response, proteins from cytoplasmic, nuclear and membrane fractions of host cells were studied by two-dimensional differential gel electrophoresis and relative protein expression differences were quantitated. Differentially expressed proteins, with at least 1.5-fold expression changes and p values of 0.01 or less, were identified by mass spectrometry including matrix-assisted laser desorption/ionization-MS or liquid chromatography tandem mass spectrometry. With these criteria, differential expression was detected in 16 human proteins after Y. pestis exposure and 13 human proteins after Y. pseudotuberculosis exposure, of which only two of the differentially expressed proteins identified were shared between the two exposures. Proteins identified in this study are reported to be involved in a wide spectrum of cellular functions and host defense mechanisms including apoptosis, cytoskeletal rearrangement, protein synthesis and degradation, DNA replication and transcription, metabolism, protein folding, and cell signaling. Notably, the differential expression patterns observed can distinguish the two pathogen exposures from each other and from unexposed host cells. The functions of the differentially expressed proteins identified provide insight on the different virulence and pathogenic mechanisms of Y. pestis and Y. pseudotuberculosis.
Insights
This study compared host protein changes in human cells exposed to Yersinia pestis and Yersinia pseudotuberculosis. The distinct protein expression patterns identified can differentiate between the two plague and intestinal distress pathogens.
Area of Science:
- Microbiology
- Immunology
- Proteomics
Background:
- Yersinia pestis causes plague, a severe disease, while Yersinia pseudotuberculosis causes intestinal illness.
- Despite high DNA homology, these bacteria exhibit vastly different clinical outcomes.
- Understanding host responses is key to elucidating differing virulence and pathogenesis.
Purpose of the Study:
- To characterize host protein expression changes in human monocyte U937 cells upon exposure to Y. pestis and Y. pseudotuberculosis.
- To identify host proteins involved in the differential pathogenesis of these closely related bacteria.
- To explore proteomic differences that distinguish host responses to Y. pestis and Y. pseudotuberculosis.
Main Methods:
- Global proteomic analysis of cytoplasmic, nuclear, and membrane host cell fractions.
- Two-dimensional differential gel electrophoresis (2D-DIGE) for quantifying protein expression.
- Mass spectrometry (MALDI-MS, LC-MS/MS) for identifying differentially expressed proteins (≥1.5-fold change, p≤0.01).
Main Results:
- Differential protein expression detected in 16 proteins after Y. pestis exposure and 13 after Y. pseudotuberculosis exposure.
- Only two differentially expressed proteins were common between the two pathogen exposures.
- Identified proteins are involved in diverse cellular functions, including apoptosis, cytoskeletal rearrangement, and cell signaling.
Conclusions:
- Host protein expression patterns differ significantly between Y. pestis and Y. pseudotuberculosis infections.
- These distinct proteomic profiles offer insights into the varying virulence and pathogenic mechanisms of the two Yersinia species.
- The observed differential expression can distinguish between the two pathogens and unexposed cells.
