Beta‐Lactam Antibiotics Promote Extracellular Vesicle Production of Staphylococcus aureus Through ROS‐Mediated Lipid Metabolic Reprogramming
ABSTRACT Bacterial extracellular vesicles (EVs) are natural reservoirs of biological active substances. They exhibit promising application in developing bioproducts such as vaccine, drug‐delivery system and anticancer agent. However, the low yield of naturally secreted EVs during bacterial growth is...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Journal of Extracellular Vesicles |
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| Online Access: | https://doi.org/10.1002/jev2.70077 |
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| author | Xiaonan Huang Zhen Hu Weilong Shang Juan Chen Qiwen Hu Yumin Zhou Ruolan Ding Jing Yin Mengyang Li He Liu Jianxiong Dou Huagang Peng Yifan Rao Lu Liu Yuting Wang Li Tan Yuhua Yang Jianghong Wu Chuan Xiao Yi Yang Xiancai Rao |
| author_facet | Xiaonan Huang Zhen Hu Weilong Shang Juan Chen Qiwen Hu Yumin Zhou Ruolan Ding Jing Yin Mengyang Li He Liu Jianxiong Dou Huagang Peng Yifan Rao Lu Liu Yuting Wang Li Tan Yuhua Yang Jianghong Wu Chuan Xiao Yi Yang Xiancai Rao |
| author_sort | Xiaonan Huang |
| collection | DOAJ |
| description | ABSTRACT Bacterial extracellular vesicles (EVs) are natural reservoirs of biological active substances. They exhibit promising application in developing bioproducts such as vaccine, drug‐delivery system and anticancer agent. However, the low yield of naturally secreted EVs during bacterial growth is a bottleneck factor that restricts EV applications. In this study, we showed that sub‐minimum inhibitory concentration (MIC) of β‐lactams boosted EV production in various Staphylococcus aureus strains. The expression of penicillin‐binding protein (PBP) genes increased after β‐lactam treatment, and the inactivation of alternative PBPs promoted EV secretion of S. aureus. We also demonstrated that sub‐MIC β‐lactams promoted EV production via a reactive oxygen species (ROS)‐dependent pathway. Deletion of redundant pbp genes enhanced oxacillin (OXA)‐stimulated ROS levels. Transcriptomic and lipidomic analyses revealed that OXA‐induced ROS triggered lipid metabolic reprogramming in S. aureus. Particularly, ROS promoted lipid peroxidation (LPO) and increased the biosynthesis of phosphatidic acid (PA) and lipoteichoic acid (LTA) that contributed to EV generation. Furthermore, OXA treatment altered the diversity of EV‐loaded proteins. OXA‐treated ∆agr/OXAEVs induced stronger Dengue EDIII‐specific antibodies in BALB/c mice than did ∆agrEVs. Overall, this study provided mechanic insights into β‐lactam‐promoted EV production in S. aureus, and highlighted the potential strategies to prepare EVs for various applications. |
| format | Article |
| id | doaj-art-ccc3c033b51b4f369426c8be194d5204 |
| institution | DOAJ |
| issn | 2001-3078 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj-art-ccc3c033b51b4f369426c8be194d52042025-08-20T03:12:35ZengWileyJournal of Extracellular Vesicles2001-30782025-05-01145n/an/a10.1002/jev2.70077Beta‐Lactam Antibiotics Promote Extracellular Vesicle Production of Staphylococcus aureus Through ROS‐Mediated Lipid Metabolic ReprogrammingXiaonan Huang0Zhen Hu1Weilong Shang2Juan Chen3Qiwen Hu4Yumin Zhou5Ruolan Ding6Jing Yin7Mengyang Li8He Liu9Jianxiong Dou10Huagang Peng11Yifan Rao12Lu Liu13Yuting Wang14Li Tan15Yuhua Yang16Jianghong Wu17Chuan Xiao18Yi Yang19Xiancai Rao20Department of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Pharmacy Xinqiao Hospital Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Dermatology Southwest Hospital Army Medical University Chongqing ChinaDepartment of Microbiology School of Medicine Chongqing University Chongqing ChinaDepartment of Neurology First Affiliated Hospital of Kunming Medical University Kunming ChinaDepartment of Microbiology School of Medicine Chongqing University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Emergency Medicine Xinqiao Hospital Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaDepartment of Microbiology College of Basic Medical Sciences Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing Army Medical University Chongqing ChinaABSTRACT Bacterial extracellular vesicles (EVs) are natural reservoirs of biological active substances. They exhibit promising application in developing bioproducts such as vaccine, drug‐delivery system and anticancer agent. However, the low yield of naturally secreted EVs during bacterial growth is a bottleneck factor that restricts EV applications. In this study, we showed that sub‐minimum inhibitory concentration (MIC) of β‐lactams boosted EV production in various Staphylococcus aureus strains. The expression of penicillin‐binding protein (PBP) genes increased after β‐lactam treatment, and the inactivation of alternative PBPs promoted EV secretion of S. aureus. We also demonstrated that sub‐MIC β‐lactams promoted EV production via a reactive oxygen species (ROS)‐dependent pathway. Deletion of redundant pbp genes enhanced oxacillin (OXA)‐stimulated ROS levels. Transcriptomic and lipidomic analyses revealed that OXA‐induced ROS triggered lipid metabolic reprogramming in S. aureus. Particularly, ROS promoted lipid peroxidation (LPO) and increased the biosynthesis of phosphatidic acid (PA) and lipoteichoic acid (LTA) that contributed to EV generation. Furthermore, OXA treatment altered the diversity of EV‐loaded proteins. OXA‐treated ∆agr/OXAEVs induced stronger Dengue EDIII‐specific antibodies in BALB/c mice than did ∆agrEVs. Overall, this study provided mechanic insights into β‐lactam‐promoted EV production in S. aureus, and highlighted the potential strategies to prepare EVs for various applications.https://doi.org/10.1002/jev2.70077β‐lactam antibioticsextracellular vesiclelipid metabolismpenicillin binding proteinsreactive oxygen speciesStaphylococcus aureus |
| spellingShingle | Xiaonan Huang Zhen Hu Weilong Shang Juan Chen Qiwen Hu Yumin Zhou Ruolan Ding Jing Yin Mengyang Li He Liu Jianxiong Dou Huagang Peng Yifan Rao Lu Liu Yuting Wang Li Tan Yuhua Yang Jianghong Wu Chuan Xiao Yi Yang Xiancai Rao Beta‐Lactam Antibiotics Promote Extracellular Vesicle Production of Staphylococcus aureus Through ROS‐Mediated Lipid Metabolic Reprogramming Journal of Extracellular Vesicles β‐lactam antibiotics extracellular vesicle lipid metabolism penicillin binding proteins reactive oxygen species Staphylococcus aureus |
| title | Beta‐Lactam Antibiotics Promote Extracellular Vesicle Production of Staphylococcus aureus Through ROS‐Mediated Lipid Metabolic Reprogramming |
| title_full | Beta‐Lactam Antibiotics Promote Extracellular Vesicle Production of Staphylococcus aureus Through ROS‐Mediated Lipid Metabolic Reprogramming |
| title_fullStr | Beta‐Lactam Antibiotics Promote Extracellular Vesicle Production of Staphylococcus aureus Through ROS‐Mediated Lipid Metabolic Reprogramming |
| title_full_unstemmed | Beta‐Lactam Antibiotics Promote Extracellular Vesicle Production of Staphylococcus aureus Through ROS‐Mediated Lipid Metabolic Reprogramming |
| title_short | Beta‐Lactam Antibiotics Promote Extracellular Vesicle Production of Staphylococcus aureus Through ROS‐Mediated Lipid Metabolic Reprogramming |
| title_sort | beta lactam antibiotics promote extracellular vesicle production of staphylococcus aureus through ros mediated lipid metabolic reprogramming |
| topic | β‐lactam antibiotics extracellular vesicle lipid metabolism penicillin binding proteins reactive oxygen species Staphylococcus aureus |
| url | https://doi.org/10.1002/jev2.70077 |
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