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<p>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.</p>

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Chiral peptidoglycan mimics target bacterial wall biosynthesis for pathogen intervention

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月26日

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  • Kefurong Deng,
  • Dongzhe Zou,
  • Zenan Zeng,
  • Beiling Guo,
  • Wensheng Gong,
  • Yini Xu,
  • Yachao Li,
  • Xianghui Xu

摘要

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.