Bacterial cell wall-specific nanomedicine for the elimination of Staphylococcus aureus and Pseudomonas aeruginosa through electron-mechanical intervention

Yanling You, Xu Yu, Junjie Jiang, Zhixin Chen, Ya-Xuan Zhu, Yihan Chen, Han Lin () and Jianlin Shi
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Yanling You: Chinese Academy of Medical Sciences
Xu Yu: Chinese Academy of Medical Sciences
Junjie Jiang: Shanghai University of Traditional Chinese Medicine
Zhixin Chen: Chinese Academy of Medical Sciences
Ya-Xuan Zhu: Tongji University
Yihan Chen: Chinese Academy of Medical Sciences
Han Lin: Chinese Academy of Medical Sciences
Jianlin Shi: Chinese Academy of Medical Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Personalized synergistic antibacterial agents against diverse bacterial strains are receiving increasing attention in combating antimicrobial resistance. However, the current research has been struggling to strike a balance between strain specificity and broad-spectrum bactericidal activity. Here, we propose a bacterial cell wall-specific antibacterial strategy based on an in situ engineered nanocomposite consisting of carbon substrate and decorated TiOx dots, termed TiOx@C. The fiber-like carbon substrate of TiOx@C is able to penetrate the bacterial membrane of Pseudomonas aeruginosa (P. aeruginosa), but not that of Staphylococcus aureus (S. aureus) due to its thicker bacterial wall, thus achieving bacterial wall specificity. Furthermore, a series of experiments demonstrate the specific electro-mechanical co-sterilization effect of TiOx@C. On the one hand, TiOx@C can disrupt the electron transport chain and block the energy supply of S. aureus. On the other hand, TiOx@C capable of destroying the membrane structure of P. aeruginosa could cause severe mechanical damage to P. aeruginosa as well as inducing oxidative stress and protein leakage. In vivo experiments demonstrate the efficacy of TiOx@C in eliminating 97% of bacteria in wounds and promoting wound healing in wound-infected female mice. Overall, such a bacterial cell wall-specific nanomedicine presents a promising strategy for non-antibiotic treatments for bacterial diseases.

Date: 2025
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DOI: 10.1038/s41467-025-58061-5

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