biostudies-literatureCoya JMBiotechnology and Biological Sciences Research Council927017https://www.ebi.ac.uk/biostudies/studies/S-EPMC9493720biostudies-literatureUnknown13The exploration of therapies combining antimicrobial lung proteins and conventional antibiotics is important due to the growing problem of multidrug-resistant bacteria. The aim of this study was to investigate whether human SP-A and a recombinant trimeric fragment (rfhSP-A) have cooperative antimicrobial activity with antibiotics against pathogenic Gram-negative bacteria. We found that SP-A bound the cationic peptide polymyxin B (PMB) with an apparent dissociation constant (<i>K</i> _D) of 0.32 ± 0.04 µM. SP-A showed synergistic microbicidal activity with polymyxin B and E, but not with other antibiotics, against three SP-A-resistant pathogenic bacteria: <i>Klebsiella pneumoniae</i>, non-typable <i>Haemophilus influenzae</i> (NTHi), and <i>Pseudomonas aeruginosa</i>. SP-A was notFrontiers in immunologyCooperative action of SP-A and its trimeric recombinant fragment with polymyxins against Gram-negative respiratory bacteria.PMC9493720BB/L007223/1BB/T001976/1Garcia-Fojeda BCasals CKronqvist NFraile-Agreda Vde Tapia LSaenz ABengoechea JACoya JMJohansson JfalseCooperative action of SP-A and its trimeric recombinant fragment with polymyxins against Gram-negative respiratory bacteria.The exploration of therapies combining antimicrobial lung proteins and conventional antibiotics is important due to the growing problem of multidrug-resistant bacteria. The aim of this study was to investigate whether human SP-A and a recombinant trimeric fragment (rfhSP-A) have cooperative antimicrobial activity with antibiotics against pathogenic Gram-negative bacteria. We found that SP-A bound the cationic peptide polymyxin B (PMB) with an apparent dissociation constant (<i>K</i> _D) of 0.32 ± 0.04 µM. SP-A showed synergistic microbicidal activity with polymyxin B and E, but not with other antibiotics, against three SP-A-resistant pathogenic bacteria: <i>Klebsiella pneumoniae</i>, non-typable <i>Haemophilus influenzae</i> (NTHi), and <i>Pseudomonas aeruginosa</i>. SP-A was not2022-01-01T00:00:00Z20222025-04-04T21:34:58.266Z2025-04-04T21:34:58.266ZS-EPMC94937203615983710.3389/fimmu.2022.927017