Predominantly Orphan Secretome in the Lung Pathogen Mycobacterium abscessus Revealed by a Multipronged Growth-Phase-Driven Strategy

Details

• Personal Author:
  Chandra H ; Gupta MK ; Lam Y-W ; Yadav JS
• Description:
  The emerging lung pathogen Mycobacterium abscessus is understudied for its virulence determinants and molecular targets for diagnosis and therapeutics. Here, we report a comprehensive secretome (600 proteins) of this species, which was identified using a multipronged strategy based on genetic/genomic, proteomic, and bioinformatic approaches. In-solution digested bottom-up proteomics from various growth phases identified a total of 517 proteins, while 2D-GE proteomics identified 33 proteins. A reporter-gene-fusion-based genomic library that was custom-generated in this study enabled the detection of 23 secretory proteins. A genome-wide survey for N-terminal signal sequences using bioinformatic tools (Psortb 2.0 and SignalP 3.0) combined with a strategy of the subtraction of lipoproteins and proteins containing multiple transmembrane domains yielded 116 secretory proteins. A homology search against the M. tuberculosis database identified nine additional secretory protein homologs that lacked a secretory signal sequence. Considering the little overlap (80 proteins) among the different approaches used, this study emphasized the importance of using a multipronged strategy for a comprehensive understanding of the secretome. Notably, the majority of the secreted proteins identified (over 50%) turned out to be "orphans" (those with no known functional homologs). The revelation of these species-specific orphan proteins offers a hitherto unexplored repertoire of potential targets for diagnostic, therapeutic, and vaccine research in this emerging lung pathogen. [Description provided by NIOSH]
• Subjects:
  Alveolitis, Extrinsic Allergic Lung Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Algorithms Author Keywords: Mycobacterium Abscessus Bioinformatics Bottom-up Proteomics Genomics Hypersensitivity Pneumonitis Lung Disease Lung Infections Metalworking Fluid Metalworking Fluids MWFs Mycobacterium Pathogens Secretome

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• ISSN:
  2076-2607
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 1 ; OSHA Region 5 ; Vermont
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  12
• Issue:
  2
• NIOSHTIC Number:
  nn:20069287
• Citation:
  Microorganisms 2024 Feb; 12(2):378
• Contact Point Address:
  Jagjit S. Yadav, Pulmonary/Microbial Pathogenesis Laboratory, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
• Email:
  jagjit.yadav@uc.edu
• Federal Fiscal Year:
  2024
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Microorganisms
• End Date:
  20170731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:96503b43c2d10d79d6598f9c87921054a88e33eff86e46f6647c969efcb2118ecf77a8278e9de0e0905f02b91c43556a7f9dc58e6949a46aca94d00803750b72
• Download URL:
  https://stacks.cdc.gov/view/cdc/207791/cdc_207791_DS1.pdf
• File Type:
  [PDF - 2.09 MB ]