An antibiotic-resistance conferring mutation in a neisserial porin: Structure, ion flux, and ampicillin binding

Gram-negative bacteria cause the majority of highly drug-resistant bacterial infections. To cross outer membrane complex cell envelope, antibiotics permeate through porins, trimeric channel proteins that enable exchange small polar molecules. Mutations in porins contribute to development phenotypes. In this work, we show a single point mutation porin PorB from Neisseria meningitidis, causative agent meningitis, can strongly affect binding and permeation beta-lactam antibiotics. Using X-ray crystallography, high-resolution electrophysiology, atomistic biomolecular simulation, liposome swelling experiments, demonstrate differences drug affinity, ion selectivity permeability PorB. Our work further reveals distinct interactions between transversal electric field eyelet zwitterionic drugs, which manifest themselves under applied fields electrophysiology are altered by mutation. These observations may apply more broadly drug-porin other channels. results improve molecular understanding porin-based drug-resistance bacteria.