Journal of Microbiology

, Volume 57, Issue 4, pp 288–297 | Cite as

Antimicrobial effect and proposed action mechanism of cordycepin against Escherichia coli and Bacillus subtilis

  • Qi Jiang
  • Zaixiang LouEmail author
  • Hongxin WangEmail author
  • Chen Chen
Microbial Pathogenesis and Host-Microbe Interaction


The detailed antibacterial mechanism of cordycepin efficacy against food-borne germs remains ambiguous. In this study, the antibacterial activity and action mechanism of cordycepin were assessed. The results showed that cordycepin effectively inhibited the growth of seven bacterial pathogens including both Gram-positive and Gram-negative bacterial pathogens; the minimum inhibitory concentrations (MIC) were 2.5 and 1.25 mg/ml against Escherichia coli and Bacillus subtilis, respectively. Scanning electron microscope and transmission electron microscope examination confirmed that cordycepin caused obvious damages in the cytoplasmatic membranes of both E. coli and B. subtilis. Outer membrane permeability assessment indicated the loss of barrier function and the leakage of cytoplasmic contents. Propidium iodide and carboxyfluorescein diacetate double staining approach coupled with flow cytometry analysis indicated that the integrity of cell membrane was severely damaged during a short time, while the intracellular enzyme system still remained active. This clearly suggested that membrane damage was one of the reasons for cordycepin efficacy against bacteria. Additionally, results from circular dichroism and fluorescence analysis indicated cordycepin could insert to genome DNA base and double strand, which disordered the structure of genomic DNA. Basis on these results, the mode of bactericidal action of cordycepin against E. coli and B. subtilis was found to be a dual mechanism, disrupting bacterial cell membranes and binding to bacterial genomic DNA to interfere in cellular functions, ultimately leading to cell death.


cordycepin antibacterial mechanism FCM analysis membrane disruption genomic DNA 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahn, Y.J., Park, S.J., Lee, S.G., Shin, S.C., and Choi, D.H. 2000. Cordycepin: selective growth inhibitor derived from liquid culture of Cordyceps militaris against Clostridium spp. J. Agric. Food Chem. 48, 2744–2748.CrossRefGoogle Scholar
  2. Baase, W.A. and Johnson, W.C. 1979. Circular dichroism and DNA secondary structure. Nucleic Acids Res. 6, 797–814.CrossRefGoogle Scholar
  3. Babii, C., Bahrin, L.G., Neagu, A.N., Gostin, I., Mihasan, M., Birsa, L.M., and Stefan, M. 2016. Antibacterial activity and proposed action mechanism of a new class of synthetic tricyclic flavonoids. J. Appl. Microbiol. 120, 630–637.CrossRefGoogle Scholar
  4. Bajpai, V.K., Baek, K.H., and Kang, S.C. 2012. Control of Salmonella in foods by using essential oils: A review. Food Res. Int. 45, 722–734.CrossRefGoogle Scholar
  5. Caddy, C., Giaroli, G., White, T.P., Shergill, S.S., and Tracy, D.K. 2014. Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy. Ther. Adv. Psychopharmacol. 4, 75–79.CrossRefGoogle Scholar
  6. Chang, L., Wang, J., Tong, C., Zhang, X., Zhao, L., and Liu, X. 2016. Antibacterial mechanism of polyacrylonitrile fiber with organophosphorus groups against Escherichia coli. Fibers Polym. 17, 721–728.CrossRefGoogle Scholar
  7. Cunningham, K. 1951. 508. Cordycepin, a metabolic product from cultures of Cordyceps militaris(Linn.) link. Part I. Isolation and characterisation. J. Chem. Soc. 2, 2299–2300.CrossRefGoogle Scholar
  8. Denyer, S.P. 1991. Mechanisms of action of chemical biocides. Their study and exploitation. In Denyer, S.P. and Hugo, W.B. (eds.), Society for Applied Bacteriology Technical Series 27.Google Scholar
  9. Denyer, S.P. 1995. Mechanisms of action of antibacterial biocides. Int. Biodeterior. Biodegrad. 36, 227–245.CrossRefGoogle Scholar
  10. Dewey, T.G. 1991. Biophysical and biochemical aspects of fluorescence spectroscopy. Plenum, New York, USA.CrossRefGoogle Scholar
  11. Dong, B., Almassalha, L.M., Stypula-Cyrus, Y., Urban, B.E., Chandler, J.E., Nguyen, T.Q., Sun, C., Zhang, H.F., and Backman, V. 2016. Superresolution intrinsic fluorescence imaging of chromatin utilizing native, unmodified nucleic acids for contrast. Proc. Natl. Acad. Sci. USA 113, 9716–9721.CrossRefGoogle Scholar
  12. Dorsey, J., Yentsch, C.M., Mayo, S., and Mckenna, C. 1989. Rapid analytical technique for the assessment of cell metabolic activity in marine microalgae. Cytometry 10, 622–628.CrossRefGoogle Scholar
  13. Fehlbaum, P., Bulet, P., Chernysh, S., Briand, J.P., Roussel, J.P., Letellier, L., Hetru, C., and Hoffmann, J.A. 1996. Structure-activity analysis of thanatin, a 21-residue inducible insect defense peptide with sequence homology to frog skin antimicrobial peptides. Proc. Natl. Acad. Sci. USA 93, 1221–1225.CrossRefGoogle Scholar
  14. Guerra-Rosas, M.I., Morales-Castro, J., Cubero-Márquez, M.A., Salvia-Trujillo, L., and Martín-Belloso, O. 2017. Antimicrobial activity of nanoemulsions containing essential oils and high methoxyl pectin during long-term storage. Food Control. 77, 131–138.CrossRefGoogle Scholar
  15. Hossain, M., Giri, P., and Kumar, G.S. 2008. DNA intercalation by quinacrine and methylene blue: a comparative binding and thermodynamic characterization study. DNA Cell Biol. 27, 81–90.CrossRefGoogle Scholar
  16. Hu, Z., Lee, C.I., Shah, V.K., Oh, E.H., Han, J.Y., Bae, J.R., Lee, K., Chong, M.S., Hong, J.T., and Oh, K.W. 2013. Cordycepin increases nonrapid eye movement sleep via adenosine receptors in rats. Evid. Based Complement. Alternat. Med. 2013, 840134.Google Scholar
  17. Kiduk, P. and Sungjin, C. 2010. Synthesis and antimicrobial activities of 3-O-alkyl analogues of (+)-catechin: improvement of stability and proposed action mechanism. Eur. J. Med. Chem. 45, 1028–1033.CrossRefGoogle Scholar
  18. Kim, J., Yang, C., and Dassarma, S. 1996. Analysis of left-handed Z-DNA formation in short d(CG)n sequences in Escherichia coli and Halobacterium halobium plasmids. Stabilization by increasing repeat length and DNA supercoiling but not salinity. J. Biol. Chem. 271, 9340–9346.CrossRefGoogle Scholar
  19. Kumar, C.V. and Asuncion, E.H. 1993. DNA binding studies and site selective fluorescence sensitization of an anthryl probe. J. Am. Chem. Soc. 115, 8547–8553.CrossRefGoogle Scholar
  20. Li, B., Hou, Y., Zhu, M., Bao, H., Nie, J., Zhang, G.Y., Shan, L., Yao, Y., Du, K., Yang, H., et al. 2016. 3′-Deoxyadenosine (cordycepin) produces a rapid and robust antidepressant effect via enhancing prefrontal AMPA receptor signaling pathway. Int. J. Neuropsychopharmacol. 19, pyv112.CrossRefGoogle Scholar
  21. Li, G., Wang, X., Xu, Y., Zhang, B., and Xia, X. 2013. Antimicrobial effect and mode of action of chlorogenic acid on Staphylococcus aureus. Eur. Food Res. Technol. 238, 589–596.CrossRefGoogle Scholar
  22. Lou, Z., Wang, H., Rao, S., Sun, J., Ma, C., and Li, J. 2012. p-Coumaric acid kills bacteria through dual damage mechanisms. Food Control 25, 550–554.CrossRefGoogle Scholar
  23. Lyles, J.T., Kim, A., Nelson, K., Bullard-Roberts, A.L., Hajdari, A., Mustafa, B., and Quave, C.L. 2017. The chemical and antibacterial evaluation of St. John’s wort oil macerates used in kosovar traditional medicine. Front. Microbiol. 8, 1639.CrossRefGoogle Scholar
  24. Mao, X.B., Eksriwong, T., Chauvatcharin, S., and Zhong, J.J. 2005. Optimization of carbon source and carbon/nitrogen ratio for cordycepin production by submerged cultivation of medicinal mushroom Cordyceps militaris. Process Biochem. 40, 1667–1672.CrossRefGoogle Scholar
  25. Mason, D.J., Dybowski, R., Larrick, J.W., and Gant, V.A. 1997. Antimicrobial action of rabbit leukocyte CAP18(106-137). Antimicrob. Agents Chemother. 41, 624–629.CrossRefGoogle Scholar
  26. Moreira, D., Gullon, B., Gullon, P., Gomes, A., and Tavaria, F. 2016. Bioactive packaging using antioxidant extracts for the prevention of microbial food-spoilage. Food Funct. 7, 3273–3282.CrossRefGoogle Scholar
  27. Nikolis, N., Methenitis, C., and Pneumatikakis, G. 2003. Studies on the interaction of altromycin B and its platinum(II) and palladium(II) metal complexes with calf thymus DNA and nucleotides. J. Inorg. Biochem. 95, 177–193.CrossRefGoogle Scholar
  28. Niu, G. and Tan, H. 2015. Nucleoside antibiotics: biosynthesis, regulation, and biotechnology. Trends Microbiol. 23, 110–119.CrossRefGoogle Scholar
  29. Pinto, N.D.C.C., Campos, L.M., Evangelista, A.C.S., Lemos, A.S.O., Silva, T.P., Melo, R.C.N., de Lourenço, C.C., Salvador, M.J., Apolônio, A.C.M., Scio, E., et al. 2017. Antimicrobial Annona muricata L. (soursop) extract targets the cell membranes of Grampositive and Gram-negative bacteria. Ind. Crops Prod. 107, 332–340.CrossRefGoogle Scholar
  30. Radula-Janik, K., Kopka, K., Kupka, T., and Ejsmont, K. 2014. Substituent effect of nitro group on aromaticity of carbazole rings. Chem. Heterocycl. Compd. 50, 1244–1251.CrossRefGoogle Scholar
  31. Shrestha, B., Zhang, W., Zhang, Y., and Liu, X. 2012. The medicinal fungus Cordyceps militaris: research and development. Mycol. Prog. 11, 599–614.CrossRefGoogle Scholar
  32. Stiefel, P., Schmidt-Emrich, S., Maniura-Weber, K., and Ren, Q. 2015. Critical aspects of using bacterial cell viability assays with the fluorophores SYTO9 and propidium iodide. BMC Microbiol. 15, 36–44.CrossRefGoogle Scholar
  33. Sugar, A.M. and Mccaffrey, R.P. 1998. Antifungal activity of 3′- deoxyadenosine (cordycepin). Antimicrob. Agents Chemother. 42, 1424–1427.CrossRefGoogle Scholar
  34. Tang, Y.L., Shi, Y.H., Zhao, W., Hao, G., and Le, G.W. 2008. Insertion mode of a novel anionic antimicrobial peptide MDpep5 (Val-Glu-Ser-Trp-Val) from Chinese traditional edible larvae of housefly and its effect on surface potential of bacterial membrane. J. Pharm. Biomed Anal. 48, 1187–1194.CrossRefGoogle Scholar
  35. Tuli, H.S., Sharma, A.K., Sandhu, S.S., and Kashyap, D. 2013. Cordycepin: a bioactive metabolite with therapeutic potential. Life Sci. 93, 863–869.CrossRefGoogle Scholar
  36. Zhang, R., Pang, D., and Cai, R. 1999. Interactions between DNA and DNA-targeting molecules. Chem. J. Chinese U. 20, 1210–1217.Google Scholar

Copyright information

© The Microbiological Society of Korea 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Food Science and Technology, School of Food Science and TechnologyJiangnan UniversityWuxiP. R. China
  2. 2.National Engineering Research Center for Functional FoodJiangnan UniversityWuxiP. R. China

Personalised recommendations