Gold Nanoclusters with Wavelike Chiral Lattices Interact with Outer Membrane Protein BamA to Kill Gram-Negative Bacteria through the Screw-in Effect

Resistance threatens to render antibiotics ineffective, which is posing a threat to global public health. Innovative strategies against drug-resistant bacteria are urgent. The outer membrane protein BamA, a hollow barrel with a pore of 2–4 nm, is a unique and essential structure in Gram-negative bacteria. We prepared chiral 3 nm gold nanoclusters (AuNCs) targeting BamA, exhibiting enantiomer-dependent antibacterial activity against drug-resistant Pseudomonas aeruginosa. The AuNCs with right-handed wavelike lattices (D-AuNCs) preferentially interacted with BamA through the screw-in effect, creating pores in the cell wall and resulting in bacterial death. P. aeruginosa was still susceptible to D-AuNCs due to their excellent antibiofilm activity even after 20 successive passages. D-AuNCs were applied to P. aeruginosa-infected skin wounds in mice, achieving superior wound healing compared to levofloxacin. Our work documented that chiral nanoclusters targeting BamA can efficiently kill P. aeruginosa through the screw-in effect, providing an innovative strategy to combat Gram-negative bacteria.