Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification
Abstract The emergence of multidrug-resistant bacteria (MDR), particularly in cytosolic methicillin-resistant Staphylococcus aureus (MRSA) are causing substantial infections and posing an urgent global threat to public health. The era of antibiotic resistant has hindered the development of antibioti...
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| Format: | Article |
| Language: | English |
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BMC
2025-06-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02252-6 |
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| _version_ | 1849434275576807424 |
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| author | Xiaohui Si Ruoyi Lv Ziwen Cai Zhigang Sun Wenjing Zhang Jing Wang Xiaoye Liu |
| author_facet | Xiaohui Si Ruoyi Lv Ziwen Cai Zhigang Sun Wenjing Zhang Jing Wang Xiaoye Liu |
| author_sort | Xiaohui Si |
| collection | DOAJ |
| description | Abstract The emergence of multidrug-resistant bacteria (MDR), particularly in cytosolic methicillin-resistant Staphylococcus aureus (MRSA) are causing substantial infections and posing an urgent global threat to public health. The era of antibiotic resistant has hindered the development of antibiotics that solely target bacteria, highlighting the need for alternative therapeutic strategies. Host-acting therapies are emerging as a dominant approach to address the shortage of novel antibiotics and prevent novel-resistant bacteria. Herein, we explored the modes of action of five flavonoids that combat cytosolic MRSA through host-acting antibacterial effects. Both in vitro and in vivo models demonstrated the efficacy of flavonoids in combating cytosolic MRSA lung infections. Transcriptomic and proteomic analyses revealed that the antibacterial targets of these flavonoids are linked to the phagosome pathway. Mechanistic studies further showed that flavonoids enhance lysosomal acidification, identifying it as a viable target for host-acting antibacterial drugs. These findings suggest that flavonoid treatments represent a promising host-acting therapeutic strategy for combating cytosolic MRSA infections. |
| format | Article |
| id | doaj-art-72a38c79fbe54bfa979170b1b29aa086 |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-72a38c79fbe54bfa979170b1b29aa0862025-08-20T03:26:43ZengBMCCell Communication and Signaling1478-811X2025-06-0123111510.1186/s12964-025-02252-6Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidificationXiaohui Si0Ruoyi Lv1Ziwen Cai2Zhigang Sun3Wenjing Zhang4Jing Wang5Xiaoye Liu6Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of AgricultureBeijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of AgricultureBeijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of AgricultureBeijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of AgricultureAnimal Science and Technology College, Beijing University of AgricultureBeijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of AgricultureBeijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of AgricultureAbstract The emergence of multidrug-resistant bacteria (MDR), particularly in cytosolic methicillin-resistant Staphylococcus aureus (MRSA) are causing substantial infections and posing an urgent global threat to public health. The era of antibiotic resistant has hindered the development of antibiotics that solely target bacteria, highlighting the need for alternative therapeutic strategies. Host-acting therapies are emerging as a dominant approach to address the shortage of novel antibiotics and prevent novel-resistant bacteria. Herein, we explored the modes of action of five flavonoids that combat cytosolic MRSA through host-acting antibacterial effects. Both in vitro and in vivo models demonstrated the efficacy of flavonoids in combating cytosolic MRSA lung infections. Transcriptomic and proteomic analyses revealed that the antibacterial targets of these flavonoids are linked to the phagosome pathway. Mechanistic studies further showed that flavonoids enhance lysosomal acidification, identifying it as a viable target for host-acting antibacterial drugs. These findings suggest that flavonoid treatments represent a promising host-acting therapeutic strategy for combating cytosolic MRSA infections.https://doi.org/10.1186/s12964-025-02252-6FlavonoidsHost-acting antibacterial drugsResistant bacteriaCytosolic MRSAPhagosome acidification |
| spellingShingle | Xiaohui Si Ruoyi Lv Ziwen Cai Zhigang Sun Wenjing Zhang Jing Wang Xiaoye Liu Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification Cell Communication and Signaling Flavonoids Host-acting antibacterial drugs Resistant bacteria Cytosolic MRSA Phagosome acidification |
| title | Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification |
| title_full | Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification |
| title_fullStr | Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification |
| title_full_unstemmed | Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification |
| title_short | Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification |
| title_sort | natural flavonoids combat cytosolic mrsa by potentiating phagosome acidification |
| topic | Flavonoids Host-acting antibacterial drugs Resistant bacteria Cytosolic MRSA Phagosome acidification |
| url | https://doi.org/10.1186/s12964-025-02252-6 |
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