Applied Microbiology and Biotechnology

, Volume 100, Issue 12, pp 5505–5514 | Cite as

Antibacterial activity of curcumin via apoptosis-like response in Escherichia coli

  • Dae Gyu Yun
  • Dong Gun Lee
Applied microbial and cell physiology


Curcumin, a naturally occurring phenolic compound, has been shown to exhibit antimicrobial activity against Candida albicans, Escherichia coli, Pseudomonas aeruginosa, etc., but the mechanism remains unclear. The present study was designed to investigate the novel antibacterial mechanism of curcumin that shows an apoptosis-like response in E. coli. We found that curcumin induces membrane damage at relatively high concentrations, but there was no effect at the minimum inhibitory concentration (MIC). At the MIC, curcumin-treated cells displayed various apoptotic markers such as reactive oxygen species (ROS) accumulation, membrane depolarization, and Ca2+ influx. Expression of RecA protein, which mediates a bacterial apoptosis-like response, was also increased by curcumin. In order to evaluate the influence of RecA on the appearance of other apoptotic markers, phosphatidylserine (PS) exposure and DNA fragmentation were examined and compared with a RecA deletion strain (ΔRecA). These markers were detected in E. coli wild-type cells, but not in ΔRecA cells. In conclusion, our data demonstrate that curcumin induces an apoptosis-like response in E. coli that involves RecA.


Apoptosis-like response Curcumin Escherichia coli RecA 



This work was supported by a grant from the National Research Foundation of Korea (NRF), funded by the government of Korea (MSIP) (No. 2015R1A5A6001906). KEIO ΔRecA was provided by Prof. Dong-Woo Lee (Kyungpook National University).

Compliance with ethical standards

This article does not contain any studies with human or animals subjects.

Conflict of interest

The authors declare that they have no competing interests.


  1. Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41:40–59CrossRefPubMedPubMedCentralGoogle Scholar
  2. Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006) Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2. doi: 10.1038/msb4100050
  3. Bax R, Mullan N, Verhoef J (2000) The millennium bugs—the need for and development of new antibacterials. Int J Antimicrob Agents 16:51–59CrossRefPubMedGoogle Scholar
  4. Belenky P, Ye JD, Porter CB, Cohen NR, Lobritz MA, Ferrante T, Jain S, Korry BJ, Schwarz EG, Walker GC, Collins JJ (2015) Bactericidal antibiotics induce toxic metabolic perturbations that lead to cellular damage. Cell Rep 3:968–980CrossRefGoogle Scholar
  5. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMedGoogle Scholar
  6. Cho J, Lee DG (2011) The characteristic region of arenicin-1 involved with a bacterial membrane targeting mechanism. Biochem Biophys Res Commun 405:422–427CrossRefPubMedGoogle Scholar
  7. Dominguez DC (2004) Calcium signaling in bacteria. Mol Microbiol 54:291–297CrossRefPubMedGoogle Scholar
  8. Dörr T, Lewis K, Vulić M (2009) SOS response induces persistence to fluoroquinolones in Escherichia coli. PLoS Genet 5:e1000760CrossRefPubMedPubMedCentralGoogle Scholar
  9. Dwyer DJ, Kohanski MA, Hayete B, Collins JJ (2007) Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli. Mol Syst Biol 3:91CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dwyer DJ, Camacho DM, Kohanski MA, Callura JM, Collins JJ (2012) Antibiotic-induced bacterial cell death exhibits physiological and biochemical hallmarks of apoptosis. Mol Cell 46:561–572CrossRefPubMedPubMedCentralGoogle Scholar
  11. Dwyer DJ, Belenky PA, Yang JH, MacDonald IC, Martell JD, Takahashi N, Chan CT, Lobritz MA, Braff D, Schwarz EG, Ye JD, Pati M, Vercruysse M, Ralifo PS, Allison KR, Khalil AS, Ting AY, Walker GC, Collins JJ (2014) Antibiotics induce redox-related physiological alterations as part of their lethality. PNAS 111:E2100–E2109CrossRefPubMedPubMedCentralGoogle Scholar
  12. Echave P, Tamarit J, Cabiscol E, Ros J (2003) Novel antioxidant role of alcohol dehydrogenase E from Escherichia coli. J Biol Chem 278:30193–30198CrossRefPubMedGoogle Scholar
  13. Edinger AL, Thompson CB (2004) Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 16:663–669CrossRefPubMedGoogle Scholar
  14. Erental A, Sharon I, Engelberg-Kulka H (2012) Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway. PLoS Biol 10:e1001281CrossRefPubMedPubMedCentralGoogle Scholar
  15. Erental A, Kalderon Z, Saada A, Smith Y, Engelberg-Kulka H (2014) Apoptosis-like death, an extreme SOS response in Escherichia coli. mBio 5:e01426–e01414CrossRefPubMedPubMedCentralGoogle Scholar
  16. Evans MD, Dizdaroglu M, Cooke MS (2004) Oxidative DNA damage and disease—induction, repair and significance. Mut Res 567:1–61CrossRefGoogle Scholar
  17. Gupta SC, Patchva S, Aggarwal BB (2013) Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 15:195–218CrossRefPubMedPubMedCentralGoogle Scholar
  18. Higuchi Y (2003) Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidative stress. Biochem Pharmacol 66:1527–1535CrossRefPubMedGoogle Scholar
  19. Hudault S, Guignot J, Servin AL (2001) Escherichia coli strains colonising the gastrointestinal tract protect germfree mice against Salmonella typhimurium infection. Gut 49:47–55CrossRefPubMedPubMedCentralGoogle Scholar
  20. Ingólfsson HI, Thakur P, Herold KF, Hobart EA, Ramsey NB, Periole X, de Jong DH, Zwama M, Yilmaz D, Hall K, Maretzky T, Hemmings HC Jr, Blobel C, Marrink SJ, Koçer A, Sack JT, Andersen OS (2014) Phytochemicals perturb membranes and promiscuously alter protein function. ACS Chem Biol 9:1788–1798CrossRefPubMedPubMedCentralGoogle Scholar
  21. Jung JI, Lim SS, Choi HJ, Cho HJ, Shin HK, Kim EJ, Chung WY, Park KK, Park JH (2006) Isoliquiritigenin induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells. J Nutr Biochem 17:689–696CrossRefPubMedGoogle Scholar
  22. Kaur S, Modi NH, Panda D, Roy N (2010) Probing the binding site of curcumin in Escherichia coli and Bacillus subtilis FtsZ-a structural insight to unveil antibacterial activity of curcumin. Eur J Med Chem 45:4209–4214CrossRefPubMedGoogle Scholar
  23. Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ (2007) A common mechanism of cellular death induced by bactericidal antibiotics. Cell 7:797–810CrossRefGoogle Scholar
  24. Kumar A, Dhamgaye S, Maurya IK, Singh A, Sharma M, Prasad R (2014) Curcumin targets cell wall integrity via calcineurin-mediated signaling in Candida albicans. Antimicrob Agents Chemother 58:167–175CrossRefPubMedPubMedCentralGoogle Scholar
  25. Lee W, Kim KJ, Lee DG (2014) A novel mechanism for the antibacterial effect of silver nanoparticles on Escherichia coli. Biometals 27:1191–1201CrossRefPubMedGoogle Scholar
  26. Little JW, Mount DW (1982) The SOS regulatory system of Escherichia coli. Cell 29:11–22CrossRefPubMedGoogle Scholar
  27. Malik P, Mukherjee TK (2014) Structure-function elucidation of antioxidative and prooxidative activities of the polyphenolic compound curcumin. Chin J Biol 2014:396708CrossRefGoogle Scholar
  28. Mann CL, Cidlowski JA (2001) Glucocorticoids regulate plasma membrane potential during rat thymocyte apoptosis in vivo and in vitro. Endocrinology 142:421–429CrossRefPubMedGoogle Scholar
  29. Mariño G, Kroemer G (2013) Mechanisms of apoptotic phosphatidylserine exposure. Cell Res 23:1247–1248CrossRefPubMedPubMedCentralGoogle Scholar
  30. Mykytczuk NC, Trevors JT, Leduc LG, Ferroni GD (2007) Fluorescence polarization in studies of bacterial cytoplasmic membrane fluidity under environmental stress. Prog Biophys Mol Biol 95:60–82CrossRefPubMedGoogle Scholar
  31. Nuding S, Fellermann K, Wehkamp J, Mueller HA, Stange EF (2006) A flow cytometric assay to monitor antimicrobial activity of defensins and cationic tissue extracts. J Microbiol Methods 65:335–345CrossRefPubMedGoogle Scholar
  32. Oda Y (1995) Inhibitory effect of curcumin on SOS functions induced by UV irradiation. Mut Res 348:67–73CrossRefGoogle Scholar
  33. Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 47:552–565CrossRefGoogle Scholar
  34. Packiavathy IA, Priya S, Pandian SK, Ravi AV (2014) Inhibition of biofilm development of uropathogens by curcumin—an anti-quorum sensing agent from Curcuma longa. Food Chem 148:453–460CrossRefPubMedGoogle Scholar
  35. Perrone GG, Tan SX, Dawes IW (2008) Reactive oxygen species and yeast apoptosis. Biochim Biophys Acta 1783:1354–1368CrossRefPubMedGoogle Scholar
  36. Shah PM (2005) The need for new therapeutic agents: what is the pipeline? Clin Microb Infect 3:36–42CrossRefGoogle Scholar
  37. Shanmugam MK, Rane G, Kanchi MM, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, Tan BK, Kumar AP, Sethi G (2015) The multifaceted role of curcumin in cancer prevention and treatment. Molecules 20:2728–2769CrossRefPubMedGoogle Scholar
  38. Sharma M, Manoharlal R, Puri N, Prasad R (2010) Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1 in Candida albicans. Biosci Rep 30:391–404CrossRefPubMedGoogle Scholar
  39. Shishodia S, Amin HM, Lai R, Aggarwal BB (2005) Curcumin (diferuloylmethane) inhibits constitutive NF-kB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem Pharmacol 70:700–713CrossRefPubMedGoogle Scholar
  40. Sondi I, Salopek-Sondi B (2004) Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria. J Colloid Interface Sci 275:177–182CrossRefPubMedGoogle Scholar
  41. Stewart AG, Harris T (1993) Adenosine inhibits platelet-activating factor, but not tumour necrosis factor-alpha-induced priming of human neutrophils. Immunology 78:152–158PubMedPubMedCentralGoogle Scholar
  42. Tesarik J, Martinez F, Rienzi L, Iacobelli M, Ubaldi F, Mendoza C, Greco E (2002) In-vitro effects of FSH and testosterone withdrawal on caspase activation and DNA fragmentation in different cell types of human seminiferous epithelium. Hum Reprod 17:1811–1819CrossRefPubMedGoogle Scholar
  43. Tyagi P, Singh M, Kumari H, Kumari A, Mukhopadhyay K (2015) Bactericidal activity of curcumin I is associated with damaging of bacterial membrane. PLoS One 10:e0121313CrossRefPubMedPubMedCentralGoogle Scholar
  44. Van den Eijnde SM, Boshart L, Baehrecke EH, De Zeeuw CI, Reutelingsperger CP, Vermeij-Keers C (1998) Cell surface exposure of phosphatidylserine during apoptosis is phylogenetically conserved. Apoptosis 3:9–16CrossRefPubMedGoogle Scholar
  45. Van Engeland M, Nieland LJ, Ramaekers FC, Schutte B, Reutelingsperger CP (1998) Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 31:1–9CrossRefPubMedGoogle Scholar
  46. VanLoock MS, Yu X, Yang S, Galkin VE, Huang H, Rajan SS, Anderson WF, Stohl EA, Seifert HS, Egelman EH (2003) Complexes of RecA with LexA and RecX differentiate between active and inactive RecA nucleoprotein filaments. J Mol Biol 17:345–354CrossRefGoogle Scholar
  47. Wang YF, Shao JJ, Zhou CH, Zhang DL, Bie XM, Lv FX, Zhang C, Lu ZX (2012) Food preservation effects of curcumin microcapsules. Food Control 27:113–117CrossRefGoogle Scholar
  48. Wigle TJ, Singleton SF (2007) Directed molecular screening for RecA ATPase inhibitors. Bioorg Med Chem Lett 17:3249–3253CrossRefPubMedPubMedCentralGoogle Scholar
  49. Yoo S, McKee BD (2004) Overexpression of Drosophila Rad51 protein (DmRad51) disrupts cell cycle progression and leads to apoptosis. Chromosoma 113:92–101CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural SciencesKyungpook National UniversityDaeguRepublic of Korea

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