Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Bavachin Suppresses Alpha-Hemolysin Expression and Protects Mice from Pneumonia Infection by Staphylococcus aureus

  • Tao, Ye (Changchun University of Chinese Medicine) ;
  • Sun, Dazhong (First School of Clinical Medicine, Guangzhou University of Chinese Medicine) ;
  • Ren, Xinran (School of Pharmaceutical Science, Jilin University) ;
  • Zhao, Yicheng (Changchun University of Chinese Medicine) ;
  • Zhang, Hengjian (Changchun University of Chinese Medicine) ;
  • Jiang, Tao (Changchun University of Chinese Medicine) ;
  • Guan, Jiyu (Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University) ;
  • Tang, Yong (Changchun University of Chinese Medicine) ;
  • Song, Wu (Changchun University of Chinese Medicine) ;
  • Li, Shuqiang (Department of Orthopedic Surgery, The First Hospital of Jilin University) ;
  • Wang, Li (Changchun University of Chinese Medicine)
  • Received : 2022.07.20
  • Accepted : 2022.09.08
  • Published : 2022.10.28
Download PDF
⟨ Previous Next ⟩

Abstract

Staphylococcus aureus (S. aureus) infection causes dramatic harm to human health as well as to livestock development. As an important virulence factor, alpha-hemolysin (hla) is critical in the process of S. aureus infection. In this report, we found that bavachin, a natural flavonoid, not only efficiently inhibited the hemolytic activity of hla, but was also capable of inhibiting it on transcriptional and translational levels. Moreover, further data revealed that bavachin had no neutralizing activity on hla, which did not affect the formation of hla heptamers and exhibited no effects on the hla thermal stability. In vitro assays showed that bavachin was able to reduce the S. aureus-induced damage of A549 cells. Thus, bavachin repressed the lethality of pneumonia infection, lung bacterial load and lung tissue inflammation in mice, providing potent protection to mice models in vivo. Our results indicated that bavachin has the potential for development as a candidate hla inhibitor against S. aureus.

Keywords

Acknowledgement

This work was supported by Jilin Science and Technology Funds (20200403101JC) and "Xinglin Scholar Project" of Changchun University of Chinese Medicine (No. QNKXJ2-2021ZR05).

References

  1. Jagielski T, Puacz E, Lisowski A, Siedlecki P, Dudziak W, Miedzobrodzki J, et al. 2014. Short communication: antimicrobial susceptibility profiling and genotyping of Staphylococcus aureus isolates from bovine mastitis in Poland. J. Dairy Sci. 97: 6122-6128. https://doi.org/10.3168/jds.2014-8321
  2. Peton V, Le Loir Y. 2014. Staphylococcus aureus in veterinary medicine. Infect. Genet. Evol. 21: 602-615. https://doi.org/10.1016/j.meegid.2013.08.011
  3. Fluit AC. 2012. Livestock-associated Staphylococcus aureus. Clin. Microbiol. Infect. 18: 735-744. https://doi.org/10.1111/j.1469-0691.2012.03846.x
  4. Cuny C, Wieler LH, Witte W. 2015. Livestock-associated MRSA: the impact on humans. Antibiotics (Basel) 4: 521-543. https://doi.org/10.3390/antibiotics4040521
  5. Nagase N, Sasaki A, Yamashita K, Shimizu A, Wakita Y, Kitai S, et al. 2002. Isolation and species distribution of staphylococci from animal and human skin. J. Vet. Med. Sci. 64: 245-250. https://doi.org/10.1292/jvms.64.245
  6. Andersson T, Blackberg A, Lood R, Erturk Bergdahl G. 2020. Development of a molecular imprinting-based surface plasmon resonance biosensor for rapid and sensitive detection of Staphylococcus aureus alpha hemolysin from human serum. Front. Cell Infect. Microbiol. 10: 571578. https://doi.org/10.3389/fcimb.2020.571578
  7. Mehndiratta PL, Bhalla P. 2014. Use of antibiotics in animal agriculture & emergence of methicillin-resistant Staphylococcus aureus (MRSA) clones: need to assess the impact on public health. Indian J. Med. Res. 140: 339-344.
  8. Wu SC, Liu F, Zhu K, Shen JZ. 2019. Natural products that target virulence factors in antibiotic-resistant Staphylococcus aureus. J. Agric. Food Chem. 67: 13195-13211. https://doi.org/10.1021/acs.jafc.9b05595
  9. Zhou KX, Li C, Chen DM, Pan YH, Tao YF, Qu W, et al. 2018. A review on nanosystems as an effective approach against infections of Staphylococcus aureus. Int. J. Nanomed. 13: 7333-7347. https://doi.org/10.2147/IJN.S169935
  10. Guo Y, Song G, Sun M, Wang J, Wang Y. 2020. Prevalence and therapies of antibiotic-resistance in Staphylococcus aureus. Front. Cell Infect. Microbiol. 10: 107. https://doi.org/10.3389/fcimb.2020.00107
  11. McGuinness WA, Malachowa N, DeLeo FR. 2017. Vancomycin resistance in Staphylococcus aureus. Yale J. Biol. Med. 90: 269-281.
  12. Huang Y, Yuan K, Tang M, Yue J, Bao L, Wu S, et al. 2021. Melatonin inhibiting the survival of human gastric cancer cells under ER stress involving autophagy and Ras-Raf-MAPK signalling. J. Cell. Mol. Med. 25: 1480-1492. https://doi.org/10.1111/jcmm.16237
  13. Banerjee R, Fernandez MG, Enthaler N, Graml C, Greenwood-Quaintance KE, Patel R. 2013. Combinations of cefoxitin plus other β-lactams are synergistic in vitro against community associated methicillin-resistant Staphylococcus aureus. Eur. J. Clin. Microbiol. Infect. Dis. 32: 827-833. https://doi.org/10.1007/s10096-013-1817-9
  14. Gao P, Ho PL, Yan B, Sze KH, Davies J, Kao RYT. 2018. Suppression of Staphylococcus aureus virulence by a small-molecule compound. Proc. Natl. Acad. Sci. USA 115: 8003-8008. https://doi.org/10.1073/pnas.1720520115
  15. Glatthardt T, Campos JCM, Chamon RC, de Sa Coimbra TF, Rocha GA, de Melo MAF, et al. 2020. Small molecules produced by commensal Staphylococcus epidermidis disrupt formation of biofilms by Staphylococcus aureus. Appl. Environ. Microbiol. 86.
  16. Raafat D, Otto M, Reppschlager K, Iqbal J, Holtfreter S. 2019. Fighting Staphylococcus aureus biofilms with monoclonal antibodies. Trends Microbiol. 27: 303-322. https://doi.org/10.1016/j.tim.2018.12.009
  17. Zhang B, Teng Z, Li X, Lu G, Deng X, Niu X, et al. 2017. Chalcone attenuates Staphylococcus aureus virulence by targeting sortase A and alpha-hemolysin. Front. Microbiol. 8: 1715. https://doi.org/10.3389/fmicb.2017.01715
  18. Dinges MM, Orwin PM, Schlievert PM. 2000. Exotoxins of Staphylococcus aureus. Clin. Microbiol. Rev. 13: 16-34. https://doi.org/10.1128/CMR.13.1.16
  19. Bubeck Wardenburg J, Patel RJ, Schneewind O. 2007. Surface proteins and exotoxins are required for the pathogenesis of Staphylococcus aureus pneumonia. Infect. Immun. 75: 1040-1044. https://doi.org/10.1128/IAI.01313-06
  20. Xiang Y, Guo Z, Zhu P, Chen J, Huang Y. 2019. Traditional Chinese medicine as a cancer treatment: modern perspectives of ancient but advanced science. Cancer Med. 8: 1958-1975. https://doi.org/10.1002/cam4.2108
  21. Hung YL, Wang SC, Suzuki K, Fang SH, Chen CS, Cheng WC, et al. 2019. Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages. Phytomedicine 59: 152785. https://doi.org/10.1016/j.phymed.2018.12.008
  22. Yang Y, Tang XL, Hao FR, Ma ZC, Wang YG, Wang LL, et al. 2018. Bavachin induces apoptosis through mitochondria' regulated ER stress pathway in HepG2 cells. Biol. Pharm. Bull. 41: 198-207. https://doi.org/10.1248/bpb.b17-00672
  23. Gilmore MS, Rauch M, Ramsey MM, Himes PR, Varahan S, Manson JM, et al. 2015. Pheromone killing of multidrug-resistant Enterococcus faecalis V583 by native commensal strains. Proc. Natl. Acad. Sci. USA 112: 7273-7278. https://doi.org/10.1073/pnas.1500553112
  24. Kumar P, Nagarajan A, Uchil PD. 2018. Analysis of cell viability by the MTT assay. Cold Spring Harb Protoc. 2018. doi: 10.1101/pdb.prot095505.
  25. Keenan DM, Pichler Hefti J, Veldhuis JD, Von Wolff M. 2020. Regulation and adaptation of endocrine axes at high altitude. Am. J. Physiol. Endocrinol. Metab. 318: E297-E309. https://doi.org/10.1152/ajpendo.00243.2019
  26. Goldmann O, Tuchscherr L, Rohde M, Medina E. 2016. Alpha-hemolysin enhances Staphylococcus aureus internalization and survival within mast cells by modulating the expression of beta1 integrin. Cell Microbiol. 18: 807-819. https://doi.org/10.1111/cmi.12550
  27. Rauch S, DeDent AC, Kim HK, Bubeck Wardenburg J, Missiakas DM, Schneewind O. 2012. Abscess formation and alpha-hemolysin induced toxicity in a mouse model of Staphylococcus aureus peritoneal infection. Infect. Immun. 80: 3721-3732. https://doi.org/10.1128/IAI.00442-12
  28. Kong C, Neoh HM, Nathan S. 2016. Targeting Staphylococcus aureus toxins: a potential form of anti-virulence therapy. Toxins 8: 72. https://doi.org/10.3390/toxins8030072
  29. Jin YH, Kim DE, Jang MS, Min JS, Kwon S. 2021. Bavachin produces immunoadjuvant activity by targeting the NFAT signaling pathway. Phytomedicine 93: 153796. https://doi.org/10.1016/j.phymed.2021.153796
  30. Chopra B, Dhingra AK, Dhar KL. 2013. Psoralea corylifolia L. (Buguchi) - Folklore to modem evidence: review. Fitoterapia 90: 44-56. https://doi.org/10.1016/j.fitote.2013.06.016
  31. Yin S, Fan CQ, Wang Y, Dong L, Yue JM. 2004. Antibacterial prenylflavone derivatives from Psoralea corylifolia, and their structureactivity relationship study. Bioorg. Med. Chem. 12: 4387-4392. https://doi.org/10.1016/j.bmc.2004.06.014
  32. Lee JH, Park JH, Cho MH, Lee J. 2012. Flavone reduces the production of virulence factors, staphyloxanthin and α-hemolysin, in Staphylococcus aureus. Curr. Microbiol. 65: 726-732. https://doi.org/10.1007/s00284-012-0229-x
  33. Cho HS, Lee JH, Cho MH, Lee J. 2015. Red wines and flavonoids diminish Staphylococcus aureus virulence with anti-biofilm and anti-hemolytic activities. Biofouling. 31: 1-11. https://doi.org/10.1080/08927014.2014.991319
  34. Lee JH, Park JH, Cho HS, Joo SW, Cho MH, Lee J. 2013. Anti-biofilm activities of quercetin and tannic acid against Staphylococcus aureus. Biofouling 29: 491-499. https://doi.org/10.1080/08927014.2013.788692
  35. Fiaschi L, Di Palo B, Scarselli M, Pozzi C, Tomaszewski K, Galletti B, et al. 2016. Auto-assembling detoxified Staphylococcus aureus alpha-hemolysin mimicking the wild-type cytolytic toxin. Clin. Vaccine Immunol. 23: 442-450. https://doi.org/10.1128/CVI.00091-16
  36. Du Y, Liu L, Zhang C, Zhang Y. 2018. Two residues in Staphylococcus aureus alpha-hemolysin related to hemolysis and self-assembly. Infect. Drug Resist. 11: 1271-1274. https://doi.org/10.2147/IDR.S167779
  37. Kebaier C, Chamberland RR, Allen IC, Gao X, Broglie PM, Hall JD, et al. 2012. Staphylococcus aureus α-hemolysin mediates virulence in a murine model of severe pneumonia through activation of the NLRP3 inflammasome. J. Infect. Dis. 205: 807-817. https://doi.org/10.1093/infdis/jir846
  38. Montgomery CP, Boyle-Vavra S, Daum RS. 2010. Importance of the global regulators Agr and SaeRS in the pathogenesis of CAMRSA USA300 infection. PLoS One 5: e15177. https://doi.org/10.1371/journal.pone.0015177
  39. George EA, Novick RP, Muir TW. 2008. Cyclic peptide inhibitors of staphylococcal virulence prepared by Fmoc-based thiolactone peptide synthesis. J. Am. Chem. Soc. 130: 4914-4924. https://doi.org/10.1021/ja711126e
  40. Matsumoto M, Nakagawa S, Zhang L, Nakamura Y, Villaruz AE, Otto M, et al. 2021. Interaction between Staphylococcus Agr virulence and neutrophils regulates pathogen expansion in the skin. Cell Host Microbe 29: 930-940.e4. https://doi.org/10.1016/j.chom.2021.03.007
  41. Fu Y, Yang Z, Zhang H, Liu Y, Hao B, Shang R. 2021. 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin inhibits alphahemolysin and protects Raw264.7 cells from injury induced by methicillin-resistant S. aureus. Microb. Pathog. 161: 105229. https://doi.org/10.1016/j.micpath.2021.105229