Institute of Clinical Microbiology and Hygiene Regensburg, University Hospital Regensburg, Regensburg, Germany
Martina Toelge
Institute of Clinical Microbiology and Hygiene Regensburg, University Hospital Regensburg, Regensburg, Germany
Maren Werner
Institute of Clinical Microbiology and Hygiene Regensburg, University Hospital Regensburg, Regensburg, Germany
Katharina Ursula Ederer
Institute of Clinical Microbiology and Hygiene Regensburg, University Hospital Regensburg, Regensburg, Germany
Heiko Ingo Siegmund
Institute of Pathology, University of Regensburg, Regensburg, Germany
David Peterhoff
Institute of Clinical Microbiology and Hygiene Regensburg, University Hospital Regensburg, Regensburg, Germany; Institute of Medical Microbiology and Hygiene Regensburg, University of Regensburg, Regensburg, Germany
Stefan Helmut Blaas
Department of Pneumology, Donaustauf Hospital, Donaustauf, Germany
Division of Bioanalytical Chemistry, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany
Christoph Brochhausen
Institute of Pathology, University of Regensburg, Regensburg, Germany; Institute of Pathology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Institute of Clinical Microbiology and Hygiene Regensburg, University Hospital Regensburg, Regensburg, Germany; Institute of Medical Microbiology and Hygiene Regensburg, University of Regensburg, Regensburg, Germany
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.
