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Transcriptomic and Molecular Docking Analysis Reveal Virulence Gene Regulation-Mediated Antibacterial Effects of Benzyl Isothiocyanate Against Staphylococcus aureus

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Abstract

Staphylococcus aureus (S. aureus) is a common pathogen that can cause many serious infections. Thus, efficient and practical techniques to fight S. aureus are required. In this study, transcriptomics was used to evaluate changes in S. aureus following treatment with benzyl isothiocyanate (BITC) to determine its antibacterial action. The results revealed that the BITC at subinhibitory concentrations (1/8th MIC) treated group had 94 differentially expressed genes compared to the control group, with 52 downregulated genes. Moreover, STRING analyses were used to reveal the protein interactions encoded by 36 genes. Then, we verified three significant virulence genes by qRT-PCR, including capsular polysaccharide synthesis enzyme (cp8F), capsular polysaccharide biosynthesis protein (cp5D), and thermonuclease (nuc). Furthermore, molecular docking analysis was performed to investigate the action site of BITC with the encoded proteins of cp8F, cp5D, and nuc. The results showed that the docking fraction of BITC with selected proteins ranged from − 6.00 to − 6.60 kcal/mol, predicting the stability of these complexes. BITC forms hydrophobic, hydrogen-bonded, π-π conjugated interactions with amino acids TRP (130), GLY (10), ILE (406), LYS (368), TYR (192), and ARG (114) of these proteins. These findings will aid future research into the antibacterial effects of BITC against S. aureus.

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Data Availability

The datasets generated during and/or analyzed during the current study are available in the [GSE139494] repository [https://www.ncbi.nlm.nih.gov/search/all/?term=GSE139494].

References

  1. Aslim, B., & Yucel, N. (2008). In vitro antimicrobial activity of essential oil from endemic Origanum minutiflorum on ciprofloxacin-resistant Campylobacter spp. Food chemistry, 107(2), 602–606.

    Article  CAS  Google Scholar 

  2. Bajpai, V. K., Al-Reza, S. M., Choi, U. K., Lee, J. H., & Kang, S. C. (2009). Chemical composition, antibacterial and antioxidant activities of leaf essential oil and extracts of Metasequioa glyptostroboides Miki ex Hu. Food and Chemical Toxicology, 47(8), 1876–1883.

    Article  CAS  PubMed  Google Scholar 

  3. Bania, J., Dabrowska, A., Bystron, J., Korzekwa, K., Chrzanowska, J., & Molenda, J. (2006). Distribution of newly described enterotoxin-like genes in Staphylococcus aureus from food. International Journal of Food Microbiology, 108(1), 36–41.

    Article  CAS  PubMed  Google Scholar 

  4. Mylotte, J. M., McDermott, C., & Spooner, J. A. (1987). Prospective study of 114 consecutive episodes of Staphylococcus aureus bacteremia. Reviews of Infectious Diseases, 9(5), 891–907.

    Article  CAS  PubMed  Google Scholar 

  5. Brul, S., & Coote, P. (1999). Preservative agents in foods: Mode of action and microbial resistance mechanisms. International Journal of Food Microbiology, 50(1–2), 1–17.

    Article  CAS  PubMed  Google Scholar 

  6. Liu, H., Pei, H., Han, Z., Feng, G., & Li, D. (2015). The antimicrobial effects and synergistic antibacterial mechanism of the combination of ε-Polylysine and nisin against Bacillus subtilis. Food Control, 47, 444–450.

    Article  CAS  Google Scholar 

  7. Zhang, L.-L., Zhang, L.-F., Hu, Q.-P., Hao, D.-L., & Xu, J.-G. (2017). Chemical composition, antibacterial activity of Cyperus rotundus rhizomes essential oil against Staphylococcus aureus via membrane disruption and apoptosis pathway. Food Control, 80, 290–296.

    Article  CAS  Google Scholar 

  8. Erdoğan Eliuz, E. A. (2021). Antibacterial activity and antibacterial mechanism of ethanol extracts of Lentinula edodes (Shiitake) and Agaricus bisporus (button mushroom). International Journal of Environmental Health Research, 32(8), 1824–1841.

  9. Gharehpapagh, A. C., Farahpour, M. R., & Jafarirad, S. (2021). The biological synthesis of gold/perlite nanocomposite using Urtica dioica extract and its chitosan-capped derivative for healing wounds infected with methicillin-resistant Staphylococcus aureus. International Journal of Biological Macromolecules, 183, 447–456.

    Article  Google Scholar 

  10. Kang, J., Jin, W., Wang, J., Sun, Y., Wu, X., & Liu, L. (2019). Antibacterial and anti-biofilm activities of peppermint essential oil against Staphylococcus aureus. LWT, 101, 639–645.

    Article  CAS  Google Scholar 

  11. Zhang, Y., Liu, X., Wang, Y., Jiang, P., & Quek, S. (2016). Antibacterial activity and mechanism of cinnamon essential oil against Escherichia coli and Staphylococcus aureus. Food Control, 59, 282–289.

    Article  CAS  Google Scholar 

  12. Rahman, A., & Kang, S. C. (2009). In vitro control of food-borne and food spoilage bacteria by essential oil and ethanol extracts of Lonicera japonica Thunb. Food Chemistry, 116(3), 670–675.

    Article  CAS  Google Scholar 

  13. Lee, J. H., Chung, H., Shin, Y. P., et al. (2021). In silico strategic curation, retrieval and prediction of novel antimicrobial peptide from Locusta migratoria transcriptome. Journal of Asia-Pacific Entomology, 24(2), 237–242.

    Article  Google Scholar 

  14. Pietiäinen, M., François, P., Hyyryläinen, H.-L., et al. (2009). Transcriptome analysis of the responses of Staphylococcus aureus to antimicrobial peptides and characterization of the roles of vraDE and vraSR in antimicrobial resistance. BMC Genomics, 10(1), 1–15.

    Article  Google Scholar 

  15. Wang, X. N., Wu, H. Y., Niu, T. X., et al. (2019). Downregulated expression of virulence factors induced by benzyl isothiocyanate in Staphylococcus Aureus: A transcriptomic analysis. International Journal of Molecular Sciences, 20, 5441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Verkerk, R., Schreiner, M., Krumbein, A., et al. (2009). Glucosinolates in Brassica vegetables: The influence of the food supply chain on intake, bioavailability and human health. Molecular Nutrition & Food Research, 53(S2), S219–S219.

    Article  Google Scholar 

  17. Morse, M. A., Zu, H., Galati, A. J., Schmidt, C. J., & Stoner, G. D. (1993). Dose-related inhibition by dietary phenethyl isothiocyanate of esophageal tumorigenesis and DNA methylation induced by N-nitrosomethylbenzylamine in rats. Cancer Letters, 72(1–2), 103–110.

    Article  CAS  PubMed  Google Scholar 

  18. Borges, A., Abreu, A. C., Ferreira, C., Saavedra, M. J., Simões, L. C., & Simões, M. (2015). Antibacterial activity and mode of action of selected glucosinolate hydrolysis products against bacterial pathogens. Journal of Food Science and Technology, 52(8), 4737–4748.

    Article  CAS  PubMed  Google Scholar 

  19. Kaiser, S. J., Mutters, N. T., Blessing, B., & Günther, F. (2017). Natural isothiocyanates express antimicrobial activity against developing and mature biofilms of Pseudomonas aeruginosa. Fitoterapia, 119, 57–63.

    Article  CAS  PubMed  Google Scholar 

  20. Song, J., Hou, H.-M., Wu, H.-Y., et al. (2019). Transcriptomic analysis of Vibrio parahaemolyticus reveals different virulence gene expression in response to benzyl isothiocyanate. Molecules, 24(4), 761.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Niu, T.-X., Wang, X.-N., Wu, H.-Y., et al. (2020). Transcriptomic analysis, motility and biofilm formation characteristics of Salmonella typhimurium exposed to benzyl isothiocyanate treatment. International Journal of Molecular Sciences, 21(3), 1025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ajith, M. P., Abhinav, A. K. T., Ilora, G., & Paulraj, R. (2024). Biogenic carbon dots: A novel mechanistic approach to combat multidrug-resistant critical pathogens on the global priority list†. Journal of Materials Chemistry B, 12, 202–221.

    Article  Google Scholar 

  23. Ashapurna, K., Abhinav, P., Himadri, G. B., Amiya, K. P., Mani, S., Madhavan, Y., Muthupandian, S., & Ramovatar, M. (2022). Evaluation of antimicrobial, anticancer potential and Flippase induced leakage in model membrane of Centella asiatica fabricated MgONPs. Biomaterials Advances, 138, 212855.

    Article  Google Scholar 

  24. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 25(4), 402–408.

    Article  CAS  PubMed  Google Scholar 

  25. Jesudass, J. S., Kulanthaivel, S. R., Ramasamy, V., et al. (2021). In-silico protein-ligand docking studies against the estrogen protein of breast cancer using pharmacophore based virtual screening approaches. Saudi Journal of Biological Sciences, 28(1), 400–407.

    Article  Google Scholar 

  26. Aayush, G., & Zhou, H. X. (2021). Machine learning-enabled pipeline for large-scale virtual drug screening. Journal of Chemical Information and Modeling, 61(9), 4236–4244.

    Article  Google Scholar 

  27. Kitchen, D. B., Decornez, H., Furr, J. R., & Bajorath, J. (2004). Docking and scoring in virtual screening for drug discovery: Methods and applications. Nature Reviews Drug Discovery, 3(11), 935–949.

    Article  CAS  PubMed  Google Scholar 

  28. Abhirami, R., Nils, W., Jessica, C. M., & Nadeem, R. (2020). Protein-Protein interactions uncover candidate ‘core genes’ within omnigenic disease networks. PLoS Genetics, 16(7), e1008903.

    Article  Google Scholar 

  29. Yu, J., Jiang, F., Zhang, F., et al. (2021). Thermonucleases contribute to Staphylococcus aureus biofilm formation in implant-associated infections–A redundant and complementary story. Frontiers in Microbiology, 12, 687888.

  30. Zhao, M., Qin, C., Li, L., et al. (2020). Conjugation of synthetic trisaccharide of Staphylococcus aureus type 8 capsular polysaccharide elicits antibodies recognizing intact bacterium. Frontiers in chemistry, 8, 258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Qiu, J., Li, H., Meng, H., Hu, C., Li, J., Luo, M., et al. (2011). Impact of luteolin on the production of alpha-toxin by Staphylococcus aureus. Letters in Applied Microbiology, 53(2), 238–243.

    Article  CAS  PubMed  Google Scholar 

  32. Liu, L., Shen, X. F., Yu, J. Y., Cao, X. W., Zhan, Q., Guo, Y. J., & Yu, F. Y. (2020). Subinhibitory concentrations of fusidic acid may reduce the virulence of S. aureus by down-regulating sarA and saeRS to reduce biofilm formation and α-Toxin Expression. Front Microbiol, 11, 25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Duan, J., Li, M., Hao, Z., et al. (2018). Subinhibitory concentrations of resveratrol reduce alpha-hemolysin production in Staphylococcus aureus isolates by downregulating saeRS. Emerging Microbes & Infections, 7(1), 1–10.

    Google Scholar 

  34. Zhang, S., Xiong, J., Lou, W., Ning, Z., Zhang, D., & Yang, J. (2019). Antimicrobial activity and action mechanism of triglycerol monolaurate on common foodborne pathogens. Food Control, 98, 113–119.

    Article  CAS  Google Scholar 

  35. Slany, M., Oppelt, J., & Cincarova, L. (2017). Formation of Staphylococcus aureus biofilm in the presence of sublethal concentrations of disinfectants studied via a transcriptomic analysis using transcriptome sequencing (RNA-seq). Applied and Environmental Microbiology, 83(24), e01643-e1717.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Dufour, V., Stahl, M., Rosenfeld, E., Stintzi, A., & Baysse, C. (2013). Insights into the mode of action of benzyl isothiocyanate on Campylobacter jejuni. Applied and Environmental Microbiology, 79(22), 6958–6968.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Murphy, E., Lin, S. L., Nunez, L., et al. (2011). Challenges for the evaluation of Staphylococcus aureus protein based vaccines: Monitoring antigenic diversity. Human Vaccines, 7(sup1), 51–59.

    Article  CAS  PubMed  Google Scholar 

  38. Nanra, J. S., Buitrago, S. M., Crawford, S., et al. (2013). Capsular polysaccharides are an important immune evasion mechanism for Staphylococcus aureus. Human Vaccines & Immunotherapeutics, 9(3), 480–487.

    Article  CAS  Google Scholar 

  39. Thakker, M., Park, J.-S., Carey, V., & Lee, J. C. (1998). Staphylococcus aureus serotype 5 capsular polysaccharide is antiphagocytic and enhances bacterial virulence in a murine bacteremia model. Infection and Immunity, 66(11), 5183–5189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Alarcon, B., Vicedo, B., & Aznar, R. (2006). PCR-based procedures for detection and quantification of Staphylococcus aureus and their application in food. Journal of Applied Microbiology, 100(2), 352–364.

    Article  CAS  PubMed  Google Scholar 

  41. Hu, Y., Meng, J., Shi, C., Hervin, K., Fratamico, P. M., & Shi, X. (2013). Characterization and comparative analysis of a second thermonuclease from Staphylococcus aureus. Microbiological Research, 168(3), 174–182.

    Article  CAS  PubMed  Google Scholar 

  42. Jing, S., Kong, X., Wang, L., et al. (2022). Quercetin reduces the virulence of S. aureus by targeting ClpP to protect mice from MRSA-induced lethal pneumonia. Microbiology Spectrum, 10(2), e02340-21.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Jing, S., Wang, L., Wang, T., et al. (2021). Myricetin protects mice against MRSA-related lethal pneumonia by targeting ClpP. Biochemical Pharmacology, 192, 114753.

    Article  CAS  PubMed  Google Scholar 

  44. Beg, M. A., Ansari, S., & Athar, F. (2020). Molecular docking studies of Calotropis gigantea phytoconstituents against Staphylococcus aureus tyrosyl-tRNA synthetase protein. Journal of Bacteriology & Mycology: Open Access, 8(3), 78–91.

    Article  Google Scholar 

  45. Li, H., Ming, X., Xu, D., et al. (2021). Transcriptome analysis and weighted gene co-expression network reveal multitarget-directed antibacterial mechanisms of benzyl isothiocyanate against Staphylococcus aureus. Journal of Agricultural and Food Chemistry, 69(39), 11733–11741.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National Key R and D Program of China (No. 2019YFC1605902), the Liaoning Provincial Natural Science Foundation of China (No. 2019-MS-021), and the Program for Innovative Talents of Higher Learning Institutions of Liaoning (No. LR2019009).

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Authors and Affiliations

  1. School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China

    Jianan Liu, Jingran Bi, Hongman Hou & Gongliang Zhang

  2. Jinkui Food Science and Technology (Dalian) Co., Ltd, Dalian, 116000, China

    Junya Zhu

  3. Department of Inorganic Nonmetallic Materials Engineering, Dalian Polytechnic University, Dalian, 116034, China

    Hongshun Hao

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Contributions

Conceptualization: Jianan Liu; methodology: Jianan Liu; formal analysis and investigation: Junya Zhu, Hongshun Hao, Jingran Bi, Hongman Hou; writing—original draft preparation: Jianan Liu; writing—review and editing: Gongliang Zhang; funding acquisition: Gongliang Zhang; resources: Gongliang Zhang; supervision: Gongliang Zhang. All authors read and approved the final manuscript.

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Correspondence to Gongliang Zhang.

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Liu, J., Zhu, J., Hao, H. et al. Transcriptomic and Molecular Docking Analysis Reveal Virulence Gene Regulation-Mediated Antibacterial Effects of Benzyl Isothiocyanate Against Staphylococcus aureus. Appl Biochem Biotechnol (2024). https://doi.org/10.1007/s12010-024-04938-y

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