Smart Peptide Turns MRSA's Own Antibiotic-Destroying Enzyme Against It by Building a Bacteria-Trapping Net

BLAP responds specifically to MRSA-secreted β-lactamase by assembling in situ into nanofibrous networks that physically trap the bacteria, preventing host cell invasion and significantly reducing infection and abscess formation in mice.

BLAP was designed with a self-assembling peptide sequence responsive to β-lactamase cleavage, inspired by human defensin-6's nanonet formation. In vitro testing confirmed β-lactamase-triggered assembly, nanonet formation around MRSA, and prevention of host cell invasion. In vivo efficacy was tested by intramuscular BLAP injection in mice with MRSA infection.

MRSA kills tens of thousands of people annually and is resistant to nearly all β-lactam antibiotics. By using the very enzyme that confers resistance as the trigger for a bacteria-trapping mechanism, this approach turns MRSA's greatest strength into its downfall — a fundamentally new strategy for combating drug-resistant infections.

Antimicrobial resistance is projected to kill 10 million people annually by 2050. This study demonstrates a paradigm shift: instead of trying to kill resistant bacteria with drugs they can destroy, use their resistance mechanism itself as the weapon trigger. The approach could be adapted for other resistance enzymes, potentially creating an entirely new class of 'resistance-responsive' antimicrobials.

Early-stage preclinical study — efficacy in humans is unproven. BLAP works by physically trapping bacteria rather than killing them, so it may need to be combined with immune clearance or other antimicrobials. Not all MRSA strains produce the same levels of β-lactamase. Manufacturing and stability of the peptide for clinical use not addressed. Only tested against one bacterial species.