2. Academic Validation
  3. Baohuoside I targets SaeR as an antivirulence strategy to disrupt MRSA biofilm formation and pathogenicity

Baohuoside I targets SaeR as an antivirulence strategy to disrupt MRSA biofilm formation and pathogenicity

  • NPJ Biofilms Microbiomes. 2025 Mar 19;11(1):45. doi: 10.1038/s41522-025-00681-2.
Yueshan Xu # 1 2,  Li Wang # 1 3,  Dongbin Guo 1,  Yueying Wang 1 2,  Xinyao Liu 1,  Yun Sun 1,  Rong Wang 1,  Luanbiao Sun 4,  Peitong Jiang 5,  Quan Liu 6,  Bingmei Wang 7 8,  Ming Yan 9 10,  Yicheng Zhao 11 12
Affiliations

Affiliations

  • 1 Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China.
  • 2 Department of Orthopedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China.
  • 3 Clinical Medical College, Changchun University of Chinese Medicine, Changchun, China.
  • 4 China-Japan Union Hospital of Jilin University, Changchun, China.
  • 5 College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China.
  • 6 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Jilin University, Changchun, China.
  • 7 Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China. bingmeiwang1970@163.com.
  • 8 Clinical Medical College, Changchun University of Chinese Medicine, Changchun, China. bingmeiwang1970@163.com.
  • 9 Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China. mingyan.ccucm@outlook.com.
  • 10 Department of Orthopedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China. mingyan.ccucm@outlook.com.
  • 11 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Jilin University, Changchun, China. yichengzhao@live.cn.
  • 12 Chinese Medicine Guangdong Laboratory, Guangdong, Hengqin, China. yichengzhao@live.cn.
  • # Contributed equally.
PMID: 40102466 DOI: 10.1038/s41522-025-00681-2
Abstract

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) represents a critical global health challenge, making the SaeRS two-component system (TCS), a key regulator of S. aureus virulence, an ideal target for novel therapeutic approaches. In this study, virtual screening and thermal shift assays identified Baohuoside I (BI), a flavonol glycoside, as a potent inhibitor of the SaeR response regulator. BI significantly attenuated S. aureus pathogenicity without bactericidal effects, suppressing the expression of key virulence factors, such as hemolysin A (Hla) and Panton-Valentine leukocidin (PVL), while modulating immune evasion pathways. Additionally, BI disrupted biofilm formation, promoting the development of porous, less structured biofilms. Biochemical assays, including EMSA, CETSA, fluorescence quenching, and SPR, confirmed strong binding interactions between SaeR and BI. In vivo, BI demonstrated therapeutic efficacy in Galleria mellonella and rat MRSA models. These findings establish BI as a promising lead for nonbactericidal therapies to combat MRSA infections and mitigate resistance.

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