A “Lung-Trap” Theranostic Strategy for Precision Management of Drug-Resistant Bacterial Pneumonia and Bacteremia

The escalating global crisis of antibiotic resistance demands the development of novel therapeutic strategies. This study proposes a "lung-trap" strategy that shifts the paradigm from systemic chemical eradication to localized physical interception and clearance. An engineered peptide conjugate, namely BTFR, selectively accumulates in the pulmonary vasculature and undergoes self-assembly into bacteria-capturing nanofibers. These nanostructures effectively entrap methicillin-resistant <i>S. aureus</i> (MRSA), prevent its dissemination, and attenuate virulence. The platform further enables real-time NIR-II imaging and exhibits potent photodynamic activity. <i>In vivo</i> studies demonstrated that BTFR efficiently captures bacteria within the lungs, significantly reduces bacterial loading, improves survival rates, and promotes tissue repair in models of MRSA-induced pneumonia and bacteremia. This approach transforms the lung from a passive site of infection into an active defense barrier, offering a promising new paradigm for the treatment of severe bacterial infections.