The global burden of microbial infections and antimicrobial resistance, coupled with the absence of precise bacterial recognition modalities, demands innovative breakthroughs in antibacterial treatment. Here, we report a chirality-specific biomimic—D-alanine-conjugated peptidoglycan mimics (D-PM)—designed for bacterial recognition. D-PM exhibits broad-spectrum, effective recognition across ESKAPE pathogens, antibiotic-resistant strains, and clinical isolates, while displaying minimal interaction with eukaryotic cells. We elucidate the bacterial recognition mechanism, wherein D-PM—act as a biosynthetic substrates—become incorporated into peptidoglycan biosynthesis. This reveals a mechanism by which macromolecular mimetics are assimilated into bacterial biosynthesis, providing insights into bacterial recognition. Beyond recognition, D-PM enables the construction of pathogen-specific imaging agents and antibiotic-targeted delivery systems. In localized and systemic infection models, D-PM achieves efficient pathogen localization, tissue penetration, and enhanced therapeutic outcomes. This work presents a molecularly engineered strategy for bacterial recognition and intervention, offering a translational approach to address the escalating threat of infectious diseases. Improved delivery of antibiotics is needed. Here, the authors report on chirality-specific peptidoglycan mimics that hijack bacterial cell wall synthesis, enabling pathogen recognition, bioimaging, and targeted antibiotic delivery while minimizing off-target effects on host cells.
Deng et al. (2026) studied this question.