Scorpionfish BPI is highly active against multiple drug-resistant <i>Pseudomonas aeruginosa</i> isolates from people with cystic fibrosis.

Abstract

Chronic pulmonary infection is a hallmark of cystic fibrosis (CF) and requires continuous antibiotic treatment. In this context, <i>Pseudomonas aeruginosa</i> (<i>Pa</i>) 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 <i>Sebastes schlegelii</i> (scoBPI) completely escaped recognition by these autoantibodies. Moreover, scoBPI exhibited high anti-inflammatory potency towards <i>Pa</i> LPS and was bactericidal against MDR <i>Pa</i> derived from PwCF at nanomolar concentrations. In conclusion, our results highlight the potential of highly active orthologous proteins of huBPI in treatment of MDR <i>Pa</i> infections, especially in the presence of BPI-ANCA.