Subcellular proteomic analysis of host-pathogen interactions using human monocytes exposed to Yersinia pestis and Yersinia pseudotuberculosis

Celia G. Zhang, Arlene D. Gonzales, Megan W. Choi, Brett A. Chromy, J. Patrick Fitch, Sandra L. McCutchen-Maloney

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1877-1888
Number of pages12
JournalProteomics
Volume5
Issue number7
DOIs
StatePublished - May 2005
Externally publishedYes

Fingerprint

Yersinia pseudotuberculosis
Yersinia pestis
Host-Pathogen Interactions
Pathogens
Proteomics
Monocytes
Proteins
Plague
Mass spectrometry
Virulence
Cell signaling
Protein folding
U937 Cells
Cytoskeletal Proteins
DNA
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Protein Folding
Liquid chromatography
Nuclear Envelope
Electrophoresis, Gel, Two-Dimensional

Keywords

  • Biomarkers
  • Host response
  • Subcellular proteomics
  • Two-dimensional fluorescence difference gel electrophoresis
  • Yersinia

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Zhang, C. G., Gonzales, A. D., Choi, M. W., Chromy, B. A., Fitch, J. P., & McCutchen-Maloney, S. L. (2005). Subcellular proteomic analysis of host-pathogen interactions using human monocytes exposed to Yersinia pestis and Yersinia pseudotuberculosis. Proteomics, 5(7), 1877-1888. https://doi.org/10.1002/pmic.200401083

Subcellular proteomic analysis of host-pathogen interactions using human monocytes exposed to Yersinia pestis and Yersinia pseudotuberculosis. / Zhang, Celia G.; Gonzales, Arlene D.; Choi, Megan W.; Chromy, Brett A.; Fitch, J. Patrick; McCutchen-Maloney, Sandra L.

In: Proteomics, Vol. 5, No. 7, 05.2005, p. 1877-1888.

Research output: Contribution to journalArticle

Zhang, Celia G. ; Gonzales, Arlene D. ; Choi, Megan W. ; Chromy, Brett A. ; Fitch, J. Patrick ; McCutchen-Maloney, Sandra L. / Subcellular proteomic analysis of host-pathogen interactions using human monocytes exposed to Yersinia pestis and Yersinia pseudotuberculosis. In: Proteomics. 2005 ; Vol. 5, No. 7. pp. 1877-1888.
@article{9b3f62b326cf43b4833b62e5cfe28fda,
title = "Subcellular proteomic analysis of host-pathogen interactions using human monocytes exposed to Yersinia pestis and Yersinia pseudotuberculosis",
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.",
keywords = "Biomarkers, Host response, Subcellular proteomics, Two-dimensional fluorescence difference gel electrophoresis, Yersinia",
author = "Zhang, {Celia G.} and Gonzales, {Arlene D.} and Choi, {Megan W.} and Chromy, {Brett A.} and Fitch, {J. Patrick} and McCutchen-Maloney, {Sandra L.}",
year = "2005",
month = "5",
doi = "10.1002/pmic.200401083",
language = "English (US)",
volume = "5",
pages = "1877--1888",
journal = "Proteomics",
issn = "1615-9853",
publisher = "Wiley-VCH Verlag",
number = "7",

}

TY - JOUR

T1 - Subcellular proteomic analysis of host-pathogen interactions using human monocytes exposed to Yersinia pestis and Yersinia pseudotuberculosis

AU - Zhang, Celia G.

AU - Gonzales, Arlene D.

AU - Choi, Megan W.

AU - Chromy, Brett A.

AU - Fitch, J. Patrick

AU - McCutchen-Maloney, Sandra L.

PY - 2005/5

Y1 - 2005/5

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Host response

KW - Subcellular proteomics

KW - Two-dimensional fluorescence difference gel electrophoresis

KW - Yersinia

UR - http://www.scopus.com/inward/record.url?scp=17244363904&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17244363904&partnerID=8YFLogxK

U2 - 10.1002/pmic.200401083

DO - 10.1002/pmic.200401083

M3 - Article

C2 - 15825148

AN - SCOPUS:17244363904

VL - 5

SP - 1877

EP - 1888

JO - Proteomics

JF - Proteomics

SN - 1615-9853

IS - 7

ER -