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Cited by 4Antimicrobial Peptides and ActivitiesBacterial biofilms and quorum sensingCystic Fibrosis Research Advances

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Scorpionfish BPI is highly active against multiple drug-resistant Pseudomonas aeruginosa isolates from people with cystic fibrosis

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Holzinger, Jonas Maurice, Toelge, Martina, Werner, Maren, Ederer, Katharina Ursula, Siegmund, Heiko Ingo, Peterhoff, David, Blaas, Stefan Helmut, Gisch, Nicolas, Brochhausen, Christoph, Gessner, André, Bülow, Sigrid·2023·eLife
DOI 10.7554/elife.86369PMC PMC10353861

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Abstract

Chronic pulmonary infection is a hallmark of cystic fibrosis (CF) and requires continuous antibiotic treatment. In this context, Pseudomonas aeruginosa ( Pa ) is of special concern since colonizing strains frequently acquire multiple drug resistance (MDR). Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived, endogenous protein with high bactericidal potency against Gram-negative bacteria. However, a significant range of people with CF (PwCF) produce anti-neutrophil cytoplasmic antibodies against BPI (BPI-ANCA), thereby neutralizing its bactericidal function. In accordance with literature, we describe that 51.0% of a total of 39 PwCF expressed BPI-ANCA. Importantly, an orthologous protein to human BPI (huBPI) derived from the scorpionfish Sebastes schlegelii (scoBPI) completely escaped recognition by these autoantibodies. Moreover, scoBPI exhibited high anti-inflammatory potency towards Pa LPS and was bactericidal against MDR Pa derived from PwCF at nanomolar concentrations. In conclusion, our results highlight the potential of highly active orthologous proteins of huBPI in treatment of MDR Pa infections, especially in the presence of BPI-ANCA.

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Metadata

Authors
Holzinger, J. M., Toelge, M., Werner, M., Ederer, K. U., Siegmund, H. I., Peterhoff, D., Blaas, S. H., Gisch, N., Brochhausen, C., Gessner, A., & Bülow, S.
Affiliations
  • University Hospital Regensburg (DE)
  • University of Regensburg (DE)
  • Klinik Donaustauf (DE)
  • Research Center Borstel - Leibniz Lung Center (DE)
  • Heidelberg University (DE)
Corresponding author
Bülow, Sigrid
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2023-07-18
Volume
12
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.86369
PMC
PMC10353861
OpenAlex
W4384626366
Cited by
4
References
3
Citations by year
2025: 1 · 2024: 3
FWCI
0.73
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Regensburg Publication Server (University of Regensburg)
Funders
  • Universitätsklinikum Regensburg
  • Universität Regensburg
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
Keywords
bactericidal/permeability-increasing protein, antineutrophil cytoplasmic antibodies, Pseudomonas aeruginosa, multidrug resistance, cystic fibrosis, black rockfish, autoantibody neutralization, lipopolysaccharide, anti-inflammatory activity, chronic lung infection
MeSH terms
Anti-Bacterial Agents, Autoantibodies, Blood Proteins, Cystic Fibrosis, Humans, Membrane Proteins, Pseudomonas aeruginosa, Pseudomonas Infections, Antibodies, Antineutrophil Cytoplasmic, Fish Proteins

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