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Nature communications
Jan 25, 2025;16 (1): 1016.

Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria.

Jia-Hong Tian, Siyuan Huang, Ze-Han Wang, Juan-Juan Li, Xianhui Song, Ze-Tao Jiang, Bing-Sen Shi, Ying-Ying Zhao, Hui-Yan Zhang, Ke-Rang Wang, Xin-Yue Hu, Xinge Zhang, Dong-Sheng Guo
Author Information
  1. Jia-Hong Tian: College of Chemistry, Nankai University, Tianjin, China.
  2. Siyuan Huang: College of Chemistry, Nankai University, Tianjin, China.
  3. Ze-Han Wang: College of Chemistry, Nankai University, Tianjin, China.
  4. Juan-Juan Li: College of Chemistry, Nankai University, Tianjin, China.
  5. Xianhui Song: College of Chemistry, Nankai University, Tianjin, China.
  6. Ze-Tao Jiang: College of Chemistry, Nankai University, Tianjin, China.
  7. Bing-Sen Shi: College of Chemistry and Materials Science, Hebei University, Baoding, China.
  8. Ying-Ying Zhao: College of Chemistry and Materials Science, Hebei University, Baoding, China.
  9. Hui-Yan Zhang: College of Chemistry and Materials Science, Hebei University, Baoding, China.
  10. Ke-Rang Wang: College of Chemistry and Materials Science, Hebei University, Baoding, China. ORCID
  11. Xin-Yue Hu: College of Chemistry, Nankai University, Tianjin, China. huxinyue@nankai.edu.cn. ORCID
  12. Xinge Zhang: College of Chemistry, Nankai University, Tianjin, China. zhangxinge@nankai.edu.cn. ORCID
  13. Dong-Sheng Guo: College of Chemistry, Nankai University, Tianjin, China. dshguo@nankai.edu.cn. ORCID
PMID: 39863571 DOI: 10.1038/s41467-025-56308-9

Abstract

Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria. This diagnostic approach executes the significant guiding missions of screening a customized host-guest drug delivery system by disclosing the rationale behind the discrimination. We design eight azocalix[4]arenes with differential active targeting, cellular internalization, and hypoxia responsiveness to penetrate cells and interact with bacteria. Loaded with fluorescent indicators, these azocalix[4]arenes form a sensor array capable of discriminating eight intracellular bacterial species without cell lysis or separation. By fingerprinting specimens collected from bacteria-infected mice, the facilitated accurate diagnosis offers valuable guidance for selecting appropriate antibiotics. Moreover, mannose-modified azocalix[4]arene (ManAC4A) is screened as a drug carrier efficiently taken up by macrophages. Doxycycline loaded with ManAC4A exhibits improved efficacy against methicillin-resistant Staphylococcus aureus-infected peritonitis. This study introduces an emerging paradigm to intracellular bacterial diagnosis and treatment, offering broad potential in combating bacterial infectious diseases.

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Grants

  1. U20A20259/National Natural Science Foundation of China (National Science Foundation of China)
  2. 22371147/National Natural Science Foundation of China (National Science Foundation of China)
  3. 22101142/National Natural Science Foundation of China (National Science Foundation of China)
  4. 21975133/National Natural Science Foundation of China (National Science Foundation of China)

MeSH Term

Animals
Mice
Humans
Methicillin-Resistant Staphylococcus aureus
Anti-Bacterial Agents
Staphylococcal Infections
Calixarenes
Peritonitis
RAW 264.7 Cells
Macrophages
Female
Mannose
Drug Carriers
Drug Delivery Systems
Bacteria

Chemicals

Anti-Bacterial Agents
Calixarenes
Mannose
Drug Carriers
Journal Article
Article has an altmetric score of 4

Word Cloud

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