Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Isovitexin, a Potential Candidate Inhibitor of Sortase A of Staphylococcus aureus USA300

  • Mu, Dan (College of Animal Science, Jilin University) ;
  • Xiang, Hua (College of Animal Science and Technology, Jilin Agricultural University) ;
  • Dong, Haisi (College of Animal Science, Jilin University) ;
  • Wang, Dacheng (College of Animal Science, Jilin University) ;
  • Wang, Tiedong (College of Animal Science, Jilin University)
  • Received : 2018.02.12
  • Accepted : 2018.07.05
  • Published : 2018.09.28
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Abstract

Staphylococcus aureus causes a broad variety of diseases. The spread of multidrug-resistant S. aureus highlights the need to develop new ways to combat S. aureus infections. Sortase A (SrtA) can anchor proteins containing LPXTG binding motifs to the bacteria surface and plays a key role in S. aureus infections, making it a promising antivirulence target. In the present study, we used a SrtA activity inhibition assay to discover that isovitexin, a Chinese herbal product, can inhibit SrtA activity with an $IC_{50}$ of $28.98{\mu}g/ml$. Using a fibrinogen-binding assay and a biofilm formation assay, we indirectly proved the SrtA inhibitory activity of isovitexin. Additionally, isovitexin treatment decreased the amount of staphylococcal protein A (SpA) on the surface of the cells. These data suggest that isovitexin has the potential to be an anti-infective drug against S. aureus via the inhibition of sortase activity.

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References

  1. Ericson JE, Popoola VO, Smith PB, Benjamin DK, Fowler VG, Jr BD, et al. 2015. Burden of invasive Staphylococcus aureus infections in hospitalized infants. JAMA Pediatr. 169: 1198-1205.
  2. Defres S, Marwick C, Nathwani D. 2009. MRSA as a cause of lung infection including airway infection, community-acquired pneumonia and hospital-acquired pneumonia. Eur. Respir. J. 34: 1470-1476. https://doi.org/10.1183/09031936.00122309
  3. Ippolito G, Leone S, Lauria FN, Nicastri E, Wenzel RP. 2010. Methicillin-resistant Staphylococcus aureus: the superbug. Int. J. Infect. Dis. 14: S7-11.
  4. Boyle-Vavra S, Daum RS. 2007. Community-acquired methicillin-resistant Staphylococcus aureus: the role of Panton-Valentine leukocidin. Lab. Invest. 87: 3-9. https://doi.org/10.1038/labinvest.3700501
  5. Zetola N, Francis JS, Nuermberger EL, Bishai WR. 2005. Community-acquired meticillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect Dis. 5: 275-286. https://doi.org/10.1016/S1473-3099(05)70112-2
  6. Woodin KA, Morrison SH. 1994. Antibiotics: mechanisms of action. Pediatr. Rev. 15: 440-447. https://doi.org/10.1542/pir.15-11-440
  7. Rasko DA, Sperandio V. 2010. Anti-virulence strategies to combat bacteria-mediated disease. Nat. Rev. Drug Discov. 9: 117-128. https://doi.org/10.1038/nrd3013
  8. Sekirov I, Tam NM, Jogova M, Robertson ML, Li Y, Lupp C, et al. 2008. Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection. Infect. Immun. 76: 4726-4736. https://doi.org/10.1128/IAI.00319-08
  9. Smeltzer MS. 2016. Staphylococcus aureus pathogenesis: the importance of reduced cytotoxicity. Trends Microbiol. 24: 681-682. https://doi.org/10.1016/j.tim.2016.07.003
  10. Foster TJ, Hook M. 1998. Surface protein adhesins of Staphylococcus aureus. Trends Microbiol. 6: 484-488. https://doi.org/10.1016/S0966-842X(98)01400-0
  11. Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ. 2008. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. Nature Rev. Microbiol. 6: 17-27. https://doi.org/10.1038/nrmicro1818
  12. Clatworthy AE, Pierson E, Hung DT. 2011. Targeting virulence: a new paradigm for antimicrobial therapy. Nat. Chem. Biol. 3: 541-548.
  13. Kruger RG, Otvos B, Frankel BA, Bentley M, Patrick Dostal A, Mccafferty DG. 2004. Analysis of the substrate specificity of the Staphylococcus aureus sortase transpeptidase SrtA. Biochemistry 43: 1541-1551. https://doi.org/10.1021/bi035920j
  14. Maresso AW, Schneewind O. 2008. Sortase as a target of anti-infective therapy. Pharmacol. Rev. 60: 128-141. https://doi.org/10.1124/pr.107.07110
  15. Silva LN, Zimmer KR, Macedo AJ, Trentin DS. 2016. Plant natural products targeting bacterial virulence factors. Chem. Rev. 116: 9162-9236. https://doi.org/10.1021/acs.chemrev.6b00184
  16. Kong C, Neoh HM, Nathan S. 2016. Targeting Staphylococcus aureus toxins: a potential form of anti-virulence therapy. Toxins (Basel) 8: 72. https://doi.org/10.3390/toxins8030072
  17. Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. 2007. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov. 6: 29-40. https://doi.org/10.1038/nrd2201
  18. He M, Min JW, Kong WL, He XH, Li JX, Peng BW. 2016. A review on the pharmacological effects of vitexin and isovitexin. Fitoterapia 115: 74-85. https://doi.org/10.1016/j.fitote.2016.09.011
  19. Ganesan K, Xu B. 2017. Molecular targets of vitexin and isovitexin in cancer therapy: a critical review. Ann. NY Acad. Sci. 1401: 102-113. https://doi.org/10.1111/nyas.13446
  20. GA D, AR S, LS B, RC B, PP M, BS V, et al. 2015. Redox-active profile characterization of remirea maritima extracts and its cytotoxic effect in mouse fibroblasts (L929) and melanoma (B16F10) cells. Molecules 20: 11699-11718. https://doi.org/10.3390/molecules200711699
  21. Lee CY, Chien YS, Chiu TH, Huang WW, Lu CC, Chiang JH, et al. 2012. Apoptosis triggered by vitexin in U937 human leukemia cells via a mitochondrial signaling pathway. Oncol. Rep. 28: 1883-1888. https://doi.org/10.3892/or.2012.2000
  22. Chen F, Liu B, Wang D, Wang L, Deng X, Bi C, et al. 2014. Role of sortase A in the pathogenesis of Staphylococcus aureus-induced mastitis in mice. FEMS Microbiol. Lett. 351: 95-103. https://doi.org/10.1111/1574-6968.12354
  23. Changsheng Lu, Zhu J, Wang Y, Umeda A, Cowmeadow RB, Lai E, et al. 2007. Staphylococcus aureus sortase A exists as a dimeric protein in vitro. Biochemistry 46: 9346-9354. https://doi.org/10.1021/bi700519w
  24. Kim ES, Kang SY, Kim YH, Lee YE, Choi NY, You YO, et al. 2015. Chamaecyparis obtusa essential oil inhibits methicillin-resistant Staphylococcus aureus biofilm formation and expression of virulence factors. J. Med. Food. 18: 810-817. https://doi.org/10.1089/jmf.2014.3309
  25. Mazmanian SK, Ton-That H, Su K, Schneewind O. 2002. An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis. Proc. Natl. Acad. Sci. USA 99: 2293-2298. https://doi.org/10.1073/pnas.032523999
  26. Ton-That H, Liu G, Mazmanian SK, Faull KF, Schneewind O. 1999. Purification and characterization of sortase, the transpeptidase that cleaves surface proteins of Staphylococcus aureus at the LPXTG motif. Proc. Natl. Acad. Sci. USA 96: 12424-12329. https://doi.org/10.1073/pnas.96.22.12424
  27. Lopes LAA, dos Santos Rodrigues JB, Magnani M, de Souza EL, de Siqueira-Junior JP. 2017. Inhibitory effects of flavonoids on biofilm formation by Staphylococcus aureus that overexpresses efflux protein genes. Microb. Pathog. 107: 193-197. https://doi.org/10.1016/j.micpath.2017.03.033
  28. Oh KB, Oh MN, Kim JG, Shin DS, Shin J. 2006. Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors. Appl. Microbiol. Biotechnol. 70: 102-106. https://doi.org/10.1007/s00253-005-0040-8
  29. Sinha B, Francois PP, Nusse O, Foti M, Hartford OM, Vaudaux P, et al. 1999. Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1. Cell. Microbiol. 1: 101-117. https://doi.org/10.1046/j.1462-5822.1999.00011.x
  30. O'Neill E, Pozzi C, Houston P, Humphreys H, Robinson DA, Loughman A, et al. 2008. A novel staphylococcus aureus biofilm phenotype mediated by the fibronectin-binding proteins, FnBPA and FnBPB. J. Bacteriol. 190: 3835-3850. https://doi.org/10.1128/JB.00167-08
  31. Asadollahi P, Farahani NN, Mirzaii M, Khoramrooz SS, Van Belkum A, Asadollahi K, et al. 2018. Distribution of the most prevalent spa types among clinical isolates of methicillin-resistant and -susceptible Staphylococcus aureus around the world: a review. Front Microbiol. 9: 163. https://doi.org/10.3389/fmicb.2018.00163
  32. Sibbald MJ, Ziebandt AK, Engelmann S, Hecker M, De JA, Harmsen HJ, et al. 2006. Mapping the pathways to staphylococcal pathogenesis by comparative secretomics. Microbiol. Mol. Biol. Rev. 70: 755-788. https://doi.org/10.1128/MMBR.00008-06
  33. Schneewind O, Mihaylova-Petkov D, Model P. 1993. Cell wall sorting signals in surface proteins of gram-positive bacteria. EMBO J. 12: 4803-4811. https://doi.org/10.1002/j.1460-2075.1993.tb06169.x
  34. Lowy FD. 1998. Staphylococcus aureus infections. N. Engl. J. Med. 339: 520-532. https://doi.org/10.1056/NEJM199808203390806
  35. Allen H, Donato J, Wang H, Cloud-Hansen K, Davies J, Handelsman J. 2010. Call of the wild: antibiotic resistance genes in natural environments. Nat. Rev. Microbiol. 8: 251-259. https://doi.org/10.1038/nrmicro2312
  36. Foster TJ, Geoghegan JA, Ganesh VK, Hook M. 2014. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 12: 49-62. https://doi.org/10.1038/nrmicro3161
  37. Geoghegan JA, Foster TJ. 2015. Cell wall-anchored surface proteins of Staphylococcus aureus: many proteins, multiple functions. Curr. Top. Microbiol. Immunol. 409: 95-120.
  38. Wang L, Bi C, Cai H, Liu B, Zhong X, Deng X, et al. 2015. The therapeutic effect of chlorogenic acid against Staphylococcus aureus infection through sortase A inhibition. Front Microbiol. 6: 1031.
  39. Kang SS, Kim JG, Lee TH, Oh KB. 2006. Flavonols inhibit sortases and sortase-mediated Staphylococcus aureus clumping to fibrinogen. Biol. Pharm. Bull. 29: 1751-1755. https://doi.org/10.1248/bpb.29.1751
  40. Yang WY, Kim CK, Ahn CH, Kim H, Shin J, Oh KB. 2016. Flavonoid glycosides inhibit sortase A and sortase A-mediated aggregation of streptococcus mutans, an oral bacterium responsible for human dental caries. J. Microbiol. Biotechnol. 26: 1566-1569. https://doi.org/10.4014/jmb.1605.05005
  41. Liu B, Chen F, Bi C, Wang L, Zhong X, Cai H, et al. 2015. Quercitrin, an inhibitor of sortase A, interferes with the adhesion of Staphylococcal aureus. Molecules 20: 6533-6543. https://doi.org/10.3390/molecules20046533
  42. Bi C, Dong X, Zhong X, Cai H, Wang D, Wang L. 2016. Acacetin protects mice from staphylococcus aureus bloodstream infection by inhibiting the activity of sortase A. Molecules 21: 1285. https://doi.org/10.3390/molecules21101285
  43. Cucarella C, Solano C, Valle J, Amorena B, Lasa I, Penades JR. 2001. Bap, a Staphylococcus aureus surface protein involved in biofilm formation. J. Bacteriol. 183: 2888-2896. https://doi.org/10.1128/JB.183.9.2888-2896.2001
  44. Corrigan RM, Rigby D, Handley P, Foster TJ. 2007. The role of Staphylococcus aureus surface protein SasG in adherence and biofilm formation. Microbiology 153: 2235-2246.
  45. Moks T, Abrahmsen L, Nilsson B, Hellman U, Sjoquist J, Uhlen M. 1986. Staphylococcal protein A consists of five IgG-binding domains. Eur. J. Biochem. 156: 637-643. https://doi.org/10.1111/j.1432-1033.1986.tb09625.x
  46. Dedent AC, Mcadow M, Schneewind O. 2007. Distribution of protein A on the surface of Staphylococcus aureus. J. Bacteriol. 189: 4473-4484. https://doi.org/10.1128/JB.00227-07
  47. Mazmanian SK, Liu G, Jensen ER, Lenoy E, Schneewind O. 2000. Staphylococcus aureus sortase mutants defective in the display of surface proteins and in the pathogenesis of animal infections. Proc. Natl. Acad. Sci. USA 97: 5510-5515. https://doi.org/10.1073/pnas.080520697

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