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In this context,\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    (\n                    <jats:italic>Pa<\/jats:italic>\n                    ) 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\n                    <jats:italic>Sebastes schlegelii<\/jats:italic>\n                    (scoBPI) completely escaped recognition by these autoantibodies. Moreover, scoBPI exhibited high anti-inflammatory potency towards\n                    <jats:italic>Pa<\/jats:italic>\n                    LPS and was bactericidal against MDR\n                    <jats:italic>Pa<\/jats:italic>\n                    derived from PwCF at nanomolar concentrations. In conclusion, our results highlight the potential of highly active orthologous proteins of huBPI in treatment of MDR\n                    <jats:italic>Pa<\/jats:italic>\n                    infections, especially in the presence of BPI-ANCA.\n                  <\/jats:p>","DOI":"10.7554\/elife.86369","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T07:15:10Z","timestamp":1686294910000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.86369","source":"Crossref","is-referenced-by-count":4,"title":["Scorpionfish BPI is highly active against multiple drug-resistant Pseudomonas aeruginosa isolates from people with cystic fibrosis"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3274-7837","authenticated-orcid":true,"given":"Jonas Maurice","family":"Holzinger","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01226dv09","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Clinical 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