Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans

Virulence. 2020 Dec;11(1):1337-1351. doi: 10.1080/21505594.2020.1824960.

Abstract

Invasive pulmonary aspergillosis (IPA) is a severe infection that is difficult to diagnose due to the ubiquitous presence of fungal spores, the underlying diseases of risk patients, and limitations of currently available markers. In this study, we performed a comprehensive liquid chromatography tandem mass spectrometry (LC-MS/MS)-based identification of host and fungal proteins expressed during IPA in mice and humans. The proteomic analysis of bronchoalveolar lavage samples of individual IPA and control cases allowed the description of common host factors that had significantly increased abundance in both infected animals and IPA patients compared to their controls. Although increased levels of these individual host proteins might not be sufficient to distinguish bacterial from fungal infection, a combination of these markers might be beneficial to improve diagnosis. We also identified 16 fungal proteins that were specifically detected during infection and may be valuable candidates for biomarker evaluation.

Keywords: Aspergillus fumigatus; Invasive aspergillosis; biomarker; fungal pulmonary infection; proteome analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers / analysis
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Bronchoalveolar Lavage Fluid / microbiology
  • Case-Control Studies
  • Chromatography, Liquid
  • Female
  • Fungal Proteins / analysis*
  • Host-Pathogen Interactions*
  • Humans
  • Invasive Pulmonary Aspergillosis / microbiology*
  • Male
  • Mice
  • Middle Aged
  • Proteins / analysis*
  • Proteome*
  • Specific Pathogen-Free Organisms
  • Tandem Mass Spectrometry

Substances

  • Biomarkers
  • Fungal Proteins
  • Proteins
  • Proteome

Grant support

This work was supported by the BMBF [Forschungscampus InfectoGnostics, project IDES, FKZ: 13GW0096E, to IDJ]; the Northern Portugal Regional Operational Programme [NORTE 2020], under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund [ERDF; NORTE-01-0145-FEDER-000013, to AC and CC]; the Fundação para a Ciência e a Tecnologia [CEECIND/04601/2017 to CC, and CEECIND/03628/2017 to AC]; the Deutsche Forschungsgemeinschaft [TRR 124 FungiNet, “Pathogenic fungi and their human host: Networks of Interaction,” DFG project number 210879364, Project INF to GP, and A5 to HS].