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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Main Authors: Xiaohui Si, Ruoyi Lv, Ziwen Cai, Zhigang Sun, Wenjing Zhang, Jing Wang, Xiaoye Liu
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Cell Communication and Signaling
Subjects:
Online Access:https://doi.org/10.1186/s12964-025-02252-6
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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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