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Neobavaisoflavone Inhibits Biofilm Formation and α-Toxin Activity of Staphylococcus aureus

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Abstract

Neobavaisoflavone had antimicrobial activities against Gram-positive multidrug-resistant (MDR) bacteria, but the effect of neobavaisoflavone on the virulence and biofilm formation of S. aureus has not been explored. The present study aimed to investigate the possible inhibitory effect of neobavaisoflavone on the biofilm formation and α-toxin activity of S. aureus. Neobavaisoflavone presented strong inhibitory effect on the biofilm formation and α-toxin activity of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains at 25 µM, but did not affect the growth of S. aureus planktonic cells. Genetic mutations were identified in four coding genes, including cell wall metabolism sensor histidine kinase walK, RNA polymerase sigma factor rpoD, tetR family transcriptional regulator, and a hypothetical protein. The mutation of WalK (K570E) protein was identified and verified in all the neobavaisoflavone-induced mutant S. aureus isolates. The ASN501, LYS504, ILE544 and GLY565 of WalK protein act as hydrogen acceptors to form four hydrogen bonds with neobavaisoflavone by molecular docking analysis, and TRY505 of WalK protein contact with neobavaisoflavone to form a pi-H bond. In conclusion, neobavaisoflavone had excellent inhibitory effect on the biofilm formation and α-toxin activity of S. aureus. The WalK protein might be a potential target of neobavaisoflavone against S. aureus.

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Data Availability

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Code Availability

The whole-genome sequencing data generated for this study can be found in the Sequence Read Archive (SRA) database under accession number PRJNA655596 (https://dataview.ncbi.nlm.nih.gov/object/PRJNA655596).

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Acknowledgements

The authors thank Weiguang Pan and Jie Lian (Department of Laboratory Medicine, Shenzhen Nanshan People’s Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen 518052, China) for helping identify and preserve the bacterial strains.

Funding

This work was supported by the following grants: National Natural Science Foundation of China (82172283); Natural Science Foundation of Guangdong Province, China (2020A1515010979, 2020A1515111146, 2021A1515011727); Shenzhen Key Medical Discipline Construction Fund (SZXK06162); Science, Technology and Innovation Commission of Shenzhen Municipality of basic research funds (JCYJ20180302144403714, JCYJ20190809144205640, JCYJ20190809110209389, JCYJ20190809151817062), the Shenzhen Nanshan District Scientific Research Program of the People’s Republic of China (No. NS2021009, NS2021066, NS2021144, NS2021140, NS2021117).

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Author notes

  1. Fang Fang, Hongbo Xu, Bao Chai, and Duoyun Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Infectious Diseases and Department of General Medicine, the Key Lab of Endogenous Infection, Shenzhen Nanshan People’s Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, 518052, China

    Fang Fang & Lei Nie

  2. Department of Critical Care Medicine and the Key Lab of Endogenous Infection, Shenzhen Nanshan People’s Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, 518052, China

    Hongbo Xu & Haigang Zhang

  3. Department of Dermatology, Shenzhen Nanshan People’s Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, 518052, China

    Bao Chai

  4. Department of Infectious Diseases and Shenzhen Key Lab of Endogenous Infection, Shenzhen Nanshan People’s Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, 518052, China

    Duoyun Li, Zewen Wen, Zhijian Yu & Jinxin Zheng

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Contributions

Contributors FF, JZ and HZ were responsible for the organization and coordination of the trial. JZ and HZ were the chief investigators and responsible for the data analysis. HX, BC, DL, LN, ZW and ZY developed the trial design. All authors contributed to the writing of the final manuscript. All members of the JZ and HZ Study Team contributed to the management or administration of the trial. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jinxin Zheng or Haigang Zhang.

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Conflict of interest

The authors declare no conflict of interest.

Ethical Approval

All procedures involving human participants were performed in accordance with the ethical standards of Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center and with the 1964 Helsinki declaration and its later amendments, and this study was approved by the ethics committee of the Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center. Isolates were collected as part of the routine clinical management of patients, according to the national guidelines in China [27]. Therefore, informed consent was not sought.

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Supplementary file1 (DOCX 12 kb)

284_2023_3355_MOESM2_ESM.tif

Supplementary file2 (TIF 912 kb) Figure S1 Effect of different concentrations of Neobavaisoflavone on the biofilm formation of S. aureus. The 4 MSSA (a) and 4 MRSA (b) strains were treated with Neobavaisoflavone from 3.125 μM to 25 μM for 24 h. Biofilm biomasses were determined by crystal violet staining. The data presented was the average of three independent experiments (mean ± SD). Compared with control, *: P<0.05; **: P<0.01; ***: P<0.001; (Student’s t test). MSSA, methicillin-sensitive S. aureus; MRSA, methicillin-resistant S.aureus;

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Fang, F., Xu, H., Chai, B. et al. Neobavaisoflavone Inhibits Biofilm Formation and α-Toxin Activity of Staphylococcus aureus. Curr Microbiol 80, 258 (2023). https://doi.org/10.1007/s00284-023-03355-4

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