Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria
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-guid...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56308-9 |
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| author | 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_facet | 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_sort | Jia-Hong Tian |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d3d52a1585294ec9bc926da61cb9d7ca |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d3d52a1585294ec9bc926da61cb9d7ca2025-01-26T12:42:05ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-025-56308-9Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteriaJia-Hong Tian0Siyuan Huang1Ze-Han Wang2Juan-Juan Li3Xianhui Song4Ze-Tao Jiang5Bing-Sen Shi6Ying-Ying Zhao7Hui-Yan Zhang8Ke-Rang Wang9Xin-Yue Hu10Xinge Zhang11Dong-Sheng Guo12College of Chemistry, Nankai UniversityCollege of Chemistry, Nankai UniversityCollege of Chemistry, Nankai UniversityCollege of Chemistry, Nankai UniversityCollege of Chemistry, Nankai UniversityCollege of Chemistry, Nankai UniversityCollege of Chemistry and Materials Science, Hebei UniversityCollege of Chemistry and Materials Science, Hebei UniversityCollege of Chemistry and Materials Science, Hebei UniversityCollege of Chemistry and Materials Science, Hebei UniversityCollege of Chemistry, Nankai UniversityCollege of Chemistry, Nankai UniversityCollege of Chemistry, Nankai UniversityAbstract 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.https://doi.org/10.1038/s41467-025-56308-9 |
| spellingShingle | 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 Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria Nature Communications |
| title | Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria |
| title_full | Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria |
| title_fullStr | Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria |
| title_full_unstemmed | Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria |
| title_short | Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria |
| title_sort | supramolecular discrimination and diagnosis guided treatment of intracellular bacteria |
| url | https://doi.org/10.1038/s41467-025-56308-9 |
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