Immunoproteomic Identification of Secretory and Subcellular Protein Antigens and Functional Evaluation of the Secretome Fraction of Mycobacterium immunogenum, a Newly Recognized Species of the Mycobacterium chelonae-Mycobacterium abscessus Group

Details

• Personal Author:
  Gupta MK ; Subramanian V ; Yadav JS
• Description:
  Mycobacterium immunogenum has been associated with occupational pulmonary disease hypersensitivity pneumonitis (HP). The aim of this study was to identify immunogenic proteins (antigens) in this pathogen as a first step toward understanding its virulence factors and role in HP etiology. Immunoproteomic profiling of secreted and subcellular protein fractions using a combination of two-dimensional electrophoresis (2-DE), immunoblotting, and matrix-assisted laser desorption/ionization-Time of flight (MALDI-TOF) led to the identification of 33 immunoreactive proteins, comprising of 4 secretory, 6 cell wall-associated, 11 membranous, and 12 cytosolic proteins. Of these, eight immunoreactive proteins represented homologues of the known mycobacterial antigens, namely heat shock protein GroEL, antigen 85A, elongation factor Tu (EF-Tu), l-asparaginase, polyketide synthase, PE-PGRS, PPE, and superoxide dismutase (SOD). Global functional search revealed that the remaining 25 novel mycobacterial antigens in M. immunogenum showed homology with hypothetical proteins (11 antigens) and other bacterial proteins (14 antigens) with a role in virulence, survival, and/or diverse metabolic functions. To understand immunogenicity of the secretome in M. immunogenum, the major protein spot on the secretome 2D-gel (consisting of multiple secretory antigens such as OtsB and CtpA, among others) was eluted and subjected to functional characterization in terms of induction of innate immune response in murine alveolar macrophages. The secretome eluate caused up-regulation of the proinflammatory cytokines TNF-a, IL-1β, IL-6, and IL-18 and down-regulation of the anti-inflammatory cytokine IL-10, implying a potential of the secreted antigens to cause host immune response underlying the M. immunogenum-induced lung disease HP. This is the first report on identification of antigens in M. immunogenum as well as on the potential of its secretome proteins to induce host response. The identified antigens could have likely roles in virulence and/or diagnosis and serve as potential targets for drug, biocide, and/or vaccine development. [Description provided by NIOSH]
• Subjects:
  Antigens Bacterial Infections Biological Factors Hazardous Substances Hypersensitivity Immune System Irritants Lung Lung Diseases Mass Spectrometry Microbiology Occupational Health Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Alveolar Macrophages Author Keywords: Mycobacterium Immunogenum Bacteria Bacterial-disease Bacterial-infections Bactericides Bacteriology Biological-effects Biological-factors Biological-systems Biological-transport Breathing Drug-receptor Drugs Health-hazards Immune-reaction Immune-system Immune Response Immunological-tests Immunology Immunoproteomics Inhalation-studies Mass-spectrometry Microbial-test-systems Microorganisms Microscopic-analysis Pulmonary-disorders Pulmonary-system Pulmonary-system-disorders Respiratory-hypersensitivity Respiratory-infections Respiratory-irritants Vaccines

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• ISSN:
  1535-3893
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  8
• Issue:
  5
• NIOSHTIC Number:
  nn:20035558
• Citation:
  J Proteome Res 2009 May; 8(5):2319-2330
• Contact Point Address:
  Dr. Jagjit Yadav, Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, 137 Kettering Laboratory, Cincinnati, OH 45267-0056
• Email:
  Jagjit.Yadav@uc.edu
• Federal Fiscal Year:
  2009
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Journal of Proteome Research
• End Date:
  20170731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d18cdc7ec744f0536852fff89855990343e39989ec9eab165082b4c0047abf11d8083a83c41c84eaf7c072eed2abf45f74b2cb04dc5590b604830b1a02380496
• Download URL:
  https://stacks.cdc.gov/view/cdc/187382/cdc_187382_DS1.pdf
• File Type:
  [PDF - 2.49 MB ]