Holzinger, Jonas Maurice and Toelge, Martina and Werner, Maren and Ederer, Katharina Ursula and Siegmund, Heiko Ingo and Peterhoff, David and Blaas, Stefan Helmut and Gisch, Nicolas and Brochhausen, Christoph and Gessner, Andre and Buelow, Sigrid (2023) Scorpionfish BPI is highly active against multiple drug-resistant <i>Pseudomonas aeruginosa</i> isolates from people with cystic fibrosis. ELIFE, 12: e86369. ISSN 2050-084X,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PERMEABILITY-INCREASING PROTEIN; INDUCED CYTOKINE RELEASE; GRAM-NEGATIVE BACTERIA; BINDING PROTEIN; LIPOPOLYSACCHARIDE; BACTERICIDAL/PERMEABILITY; NEUTROPHILS; PATHOGENESIS; CHILDREN; ELASTASE; bactericidal/permeability-increasing protein; scorpionfish; Pseudomonas aeruginosa; multiple drug resistance; cystic fibrosis; anti-neutrophil cytoplasmic antibodies |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2024 09:59 |
| Last Modified: | 08 Mar 2024 09:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59109 |
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