Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity‐Switching, Self‐Immobilizing, Near‐Infrared Fluorogenic β‐Lactamase Probe Enriched within Bacteria
Abstract The emergence of antibiotic resistance, particularly bacterial resistance to β‐lactam antibiotics, the most widely prescribed therapeutic agents for infectious diseases, poses a significant threat to public health worldwide. The discovery of effective therapies against antibiotic‐resistant...
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| Format: | Article |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408559 |
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| author | Fangfang Chen Yuyao Li Yan Peng Yifan Zhu Gao He Zhengwei Zhang Hexin Xie |
| author_facet | Fangfang Chen Yuyao Li Yan Peng Yifan Zhu Gao He Zhengwei Zhang Hexin Xie |
| author_sort | Fangfang Chen |
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| description | Abstract The emergence of antibiotic resistance, particularly bacterial resistance to β‐lactam antibiotics, the most widely prescribed therapeutic agents for infectious diseases, poses a significant threat to public health worldwide. The discovery of effective therapies against antibiotic‐resistant pathogens has become an urgent need, necessitating innovative approaches to accelerate the identification and development of novel antibacterial agents. On the other hand, the expression of the β‐lactam‐hydrolyzing enzyme (β‐lactamase), the major cause of bacterial resistance to β‐lactam antibiotics, provides a distinctive opportunity to visualize bacterial infection, evaluate the efficacy of existing antibiotics, screen for novel antibacterial agents, and optimize drug dosing regimens in live animals. Herein, a hydrophilicity‐switching, self‐immobilizing, near‐Infrared fluorogenic β‐lactamase probe for the highly sensitive imaging of bacterial infection in live mice is reported. This probe, in addition to a significant increase in fluorescence upon selective hydrolysis by β‐lactamases as conventional β‐lactamase probes, also massively enriches within β‐lactamase‐expressing bacteria (over 1500‐folds compared to the incubation medium), which renders excellent sensitivity in the imaging of bacterial infections in living animals. This agent has proven to enable the assessment of antibiotic therapeutic efficacy and potency of β‐lactamase inhibitors in living animals in a non‐invasive and much more convenient manner. |
| format | Article |
| id | doaj-art-c42c50ff3cb34a92a9c707c46df3326c |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-c42c50ff3cb34a92a9c707c46df3326c2025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202408559Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity‐Switching, Self‐Immobilizing, Near‐Infrared Fluorogenic β‐Lactamase Probe Enriched within BacteriaFangfang Chen0Yuyao Li1Yan Peng2Yifan Zhu3Gao He4Zhengwei Zhang5Hexin Xie6State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology Shanghai 200237 P.R. ChinaState Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology Shanghai 200237 P.R. ChinaState Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology Shanghai 200237 P.R. ChinaState Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology Shanghai 200237 P.R. ChinaState Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology Shanghai 200237 P.R. ChinaDepartment of Nuclear Medicine & PET Center Huashan Hospital, Fudan University Shanghai 200235 ChinaState Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology Shanghai 200237 P.R. ChinaAbstract The emergence of antibiotic resistance, particularly bacterial resistance to β‐lactam antibiotics, the most widely prescribed therapeutic agents for infectious diseases, poses a significant threat to public health worldwide. The discovery of effective therapies against antibiotic‐resistant pathogens has become an urgent need, necessitating innovative approaches to accelerate the identification and development of novel antibacterial agents. On the other hand, the expression of the β‐lactam‐hydrolyzing enzyme (β‐lactamase), the major cause of bacterial resistance to β‐lactam antibiotics, provides a distinctive opportunity to visualize bacterial infection, evaluate the efficacy of existing antibiotics, screen for novel antibacterial agents, and optimize drug dosing regimens in live animals. Herein, a hydrophilicity‐switching, self‐immobilizing, near‐Infrared fluorogenic β‐lactamase probe for the highly sensitive imaging of bacterial infection in live mice is reported. This probe, in addition to a significant increase in fluorescence upon selective hydrolysis by β‐lactamases as conventional β‐lactamase probes, also massively enriches within β‐lactamase‐expressing bacteria (over 1500‐folds compared to the incubation medium), which renders excellent sensitivity in the imaging of bacterial infections in living animals. This agent has proven to enable the assessment of antibiotic therapeutic efficacy and potency of β‐lactamase inhibitors in living animals in a non‐invasive and much more convenient manner.https://doi.org/10.1002/advs.202408559β‐lactamasesantibiotic resistancebacterial infectionsfluorescence probesin vivo imaging |
| spellingShingle | Fangfang Chen Yuyao Li Yan Peng Yifan Zhu Gao He Zhengwei Zhang Hexin Xie Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity‐Switching, Self‐Immobilizing, Near‐Infrared Fluorogenic β‐Lactamase Probe Enriched within Bacteria Advanced Science β‐lactamases antibiotic resistance bacterial infections fluorescence probes in vivo imaging |
| title | Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity‐Switching, Self‐Immobilizing, Near‐Infrared Fluorogenic β‐Lactamase Probe Enriched within Bacteria |
| title_full | Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity‐Switching, Self‐Immobilizing, Near‐Infrared Fluorogenic β‐Lactamase Probe Enriched within Bacteria |
| title_fullStr | Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity‐Switching, Self‐Immobilizing, Near‐Infrared Fluorogenic β‐Lactamase Probe Enriched within Bacteria |
| title_full_unstemmed | Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity‐Switching, Self‐Immobilizing, Near‐Infrared Fluorogenic β‐Lactamase Probe Enriched within Bacteria |
| title_short | Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity‐Switching, Self‐Immobilizing, Near‐Infrared Fluorogenic β‐Lactamase Probe Enriched within Bacteria |
| title_sort | highly sensitive in vivo imaging of bacterial infections with a hydrophilicity switching self immobilizing near infrared fluorogenic β lactamase probe enriched within bacteria |
| topic | β‐lactamases antibiotic resistance bacterial infections fluorescence probes in vivo imaging |
| url | https://doi.org/10.1002/advs.202408559 |
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