1887

Abstract

The earliest step in cell division in bacteria is the assembly of FtsZ, an essential cell division protein, into a ring at the division site. FtsZ has GTPase activity and can assemble to form protein filaments. The present work involved the study of eight phenylpropanoids (cinnamic, -coumaric, caffeic, chlorogenic, ferulic, 3,4-dimethoxycinnamic and 2,4,5-trimethoxycinnamic acids and eugenol) as inhibitors of FtsZ. Phenylpropanoids make up the majority of our diet and act as antibacterial agents. Polymerization and GTPase inhibition assays showed that chlorogenic and caffeic acids were the most active amongst these (IC of 70 and 106 µM, respectively). Circular dichroism studies indicated that chlorogenic acid perturbed the protein conformation and electron microscopy showed distorted filaments. 168 cells treated with the phenylpropanoids were longer when compared to the control. The highest binding energy was observed between chlorogenic acid and the homology modelled FtsZ, which was consistent with the experimental results. A strong negative correlation was observed between binding energy and inhibition of the polymerization ability. 3D-Quantitative structure–activity relationship studies using GTPase activity indicated that the presence of more hydrophilic groups around the 3′- and 4′-carbon increased the activity. The effect of stress-induced formation of cell filamentation has to be understood before confirming the role of phenylpropanoids as FtsZ inhibitors.

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2011-09-01
2019-10-15
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References

  1. Akiyama Y. , Kihara A. , Tokuda H. , Ito K. . ( 1996; ). FtsH (HflB) is an ATP-dependent protease selectively acting on SecY and some other membrane proteins. . J Biol Chem 271:, 31196–31201. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bernhardt T. G. , de Boer P. A. . ( 2003; ). The Escherichia coli amidase AmiC is a periplasmic septal ring component exported via the twin-arginine transport pathway. . Mol Microbiol 48:, 1171–1182. [CrossRef] [PubMed]
    [Google Scholar]
  3. Beuria T. K. , Santra M. K. , Panda D. . ( 2005; ). Sanguinarine blocks cytokinesis in bacteria by inhibiting FtsZ assembly and bundling. . Biochemistry 44:, 16584–16593. [CrossRef] [PubMed]
    [Google Scholar]
  4. Bradford M. M. . ( 1976; ). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. . Anal Biochem 72:, 248–254. [CrossRef] [PubMed]
    [Google Scholar]
  5. Braga P. C. , Sasso M. D. , Culici M. , Alfieri M. . ( 2007; ). Eugenol and thymol, alone or in combination, induce morphological alterations in the envelope of Candida albicans . . Fitoterapia 78:, 396–400. [CrossRef] [PubMed]
    [Google Scholar]
  6. Buddelmeijer N. , Beckwith J. . ( 2002; ). Assembly of cell division proteins at the E. coli cell center. . Curr Opin Microbiol 5:, 553–557. [CrossRef] [PubMed]
    [Google Scholar]
  7. Burke M. , Rajasekharan K. N. , Maruta S. , Ikebe M. . ( 1990; ). A second consensus sequence of ATP-requiring proteins resides in the 21-kDa C-terminal segment of myosin subfragment 1. . FEBS Lett 262:, 185–188. [CrossRef] [PubMed]
    [Google Scholar]
  8. Campos F. M. , Couto J. A. , Figueiredo A. R. , Tóth I. V. , Rangel A. O. S. S. , Hogg T. A. . ( 2009; ). Cell membrane damage induced by phenolic acids on wine lactic acid bacteria. . Int J Food Microbiol 135:, 144–151. [CrossRef] [PubMed]
    [Google Scholar]
  9. Cordell S. C. , Robinson E. J. H. , Lowe J. . ( 2003; ). Crystal structure of the SOS cell division inhibitor SulA and in complex with FtsZ. . Proc Natl Acad Sci U S A 100:, 7889–7894. [CrossRef] [PubMed]
    [Google Scholar]
  10. Cramer R. D. , Patterson D. E. , Bunce J. D. . ( 1988; ). Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. . J Am Chem Soc 110:, 5959–5967. [CrossRef]
    [Google Scholar]
  11. DeLano W. L. . ( 2002; ). The PyMOL Molecular Graphics System. Palo Alto, CA:: DeLano Scientific;.
    [Google Scholar]
  12. Domadia P. , Swarup S. , Bhunia A. , Sivaraman J. , Dasgupta D. . ( 2007; ). Inhibition of bacterial cell division protein FtsZ by cinnamaldehyde. . Biochem Pharmacol 74:, 831–840. [CrossRef] [PubMed]
    [Google Scholar]
  13. Domadia P. N. , Bhunia A. , Sivaraman J. , Swarup S. , Dasgupta D. . ( 2008; ). Berberine targets assembly of Escherichia coli cell division protein FtsZ. . Biochemistry 47:, 3225–3234. [CrossRef] [PubMed]
    [Google Scholar]
  14. Farr G. W. , Sternlicht H. . ( 1992; ). Site-directed mutagenesis of the GTP-binding domain of β-tubulin. . J Mol Biol 227:, 307–321. [CrossRef] [PubMed]
    [Google Scholar]
  15. Furtado G. H. , Nicolau D. P. . ( 2010; ). Overview perspective of bacterial resistance. . Expert Opin Ther Pat 20:, 1273–1276. [CrossRef] [PubMed]
    [Google Scholar]
  16. Gill A. O. , Holley R. A. . ( 2006; ). Disruption of Escherichia coli, Listeria monocytogenes and Lactobacillus sakei cellular membranes by plant oil aromatics. . Int J Food Microbiol 108:, 1–9. [CrossRef] [PubMed]
    [Google Scholar]
  17. Halgren T. A. . ( 1996; ). Merck molecular force field. III. Molecular geometries and vibrational frequencies. . J Comput Chem 17:, 553–586. [CrossRef]
    [Google Scholar]
  18. Haydon D. J. , Stokes N. R. , Ure R. , Galbraith G. , Bennett J. M. , Brown D. R. , Baker P. J. , Barynin V. V. , Rice D. W. et al. ( 2008; ). An inhibitor of FtsZ with potent and selective anti-staphylococcal activity. . Science 321:, 1673–1675. [CrossRef] [PubMed]
    [Google Scholar]
  19. Hemaiswarya S. , Doble M. . ( 2009; ). Synergistic interaction of eugenol with antibiotics against Gram negative bacteria. . Phytomedicine 16:, 997–1005. [CrossRef] [PubMed]
    [Google Scholar]
  20. Hemaiswarya S. , Doble M. . ( 2010; ). Synergistic interaction of phenylpropanoids with antibiotics against bacteria. . J Med Microbiol 59:, 1469–1476. [CrossRef] [PubMed]
    [Google Scholar]
  21. Jaiswal R. , Beuria T. K. , Mohan R. , Mahajan S. K. , Panda D. . ( 2007; ). Totarol inhibits bacterial cytokinesis by perturbing the assembly dynamics of FtsZ. . Biochemistry 46:, 4211–4220. [CrossRef] [PubMed]
    [Google Scholar]
  22. Korkina L. G. . ( 2007; ). Phenylpropanoids as naturally occurring antioxidants: from plant defense to human health. . Cell Mol Biol (Noisy-le-grand) 53:, 15–25.[PubMed]
    [Google Scholar]
  23. Löwe J. , Amos L. A. . ( 1998; ). Crystal structure of the bacterial cell-division protein FtsZ. . Nature 391:, 203–206. [CrossRef] [PubMed]
    [Google Scholar]
  24. Löwe J. , Amos L. A. . ( 1999; ). Tubulin-like protofilaments in Ca2+-induced FtsZ sheets. . EMBO J 18:, 2364–2371. [CrossRef] [PubMed]
    [Google Scholar]
  25. Lu C. , Stricker J. , Erickson H. P. . ( 2001; ). Site-specific mutations of FtsZ – effects on GTPase and in vitro assembly. . BMC Microbiol 1:, 7.[CrossRef]
    [Google Scholar]
  26. Margolin W. . ( 2005; ). FtsZ and the division of prokaryotic cells and organelles. . Nat Rev Mol Cell Biol 6:, 862–871. [CrossRef] [PubMed]
    [Google Scholar]
  27. McDonald M. , Blondeau J. M. . ( 2010; ). Emerging antibiotic resistance in ocular infections and the role of fluoroquinolones. . J Cataract Refract Surg 36:, 1588–1598. [CrossRef] [PubMed]
    [Google Scholar]
  28. Morris G. M. , Goodsell D. S. , Halliday R. S. , Huey R. , Hart W. E. , Belew R. K. , Olson A. J. . ( 1998; ). Automated docking using a Lamarckian genetic algorithm and empirical binding free energy function. . J Comput Chem 19:, 1639–1662. [CrossRef]
    [Google Scholar]
  29. Mukherjee A. , Lutkenhaus J. . ( 1999; ). Analysis of FtsZ assembly by light scattering and determination of the role of divalent metal cations. . J Bacteriol 181:, 823–832.[PubMed]
    [Google Scholar]
  30. Mukherjee A. , Saez C. , Lutkenhaus J. . ( 2001; ). Assembly of an FtsZ mutant deficient in GTPase activity has implications for FtsZ assembly and the role of the Z ring in cell division. . J Bacteriol 183:, 7190–7197. [CrossRef] [PubMed]
    [Google Scholar]
  31. Naz S. , Ahmad S. , Ajaz Rasool S. , Asad Sayeed S. , Siddiqi R. . ( 2006; ). Antibacterial activity directed isolation of compounds from Onosma hispidum . . Microbiol Res 161:, 43–48. [CrossRef] [PubMed]
    [Google Scholar]
  32. Nogales E. , Downing K. H. , Amos L. A. , Löwe J. . ( 1998; ). Tubulin and FtsZ form a distinct family of GTPases. . Nat Struct Biol 5:, 451–458. [CrossRef] [PubMed]
    [Google Scholar]
  33. Perez-Iratxeta C. , Andrade-Navarro M. A. . ( 2008; ). K2D2: estimation of protein secondary structure from circular dichroism spectra. . BMC Struct Biol 8:, 25. [CrossRef] [PubMed]
    [Google Scholar]
  34. Puupponen-Pimiä R. , Nohynek L. , Meier C. , Kähkönen M. , Heinonen M. , Hopia A. , Oksman-Caldentey K.-M. . ( 2001; ). Antimicrobial properties of phenolic compounds from berries. . J Appl Microbiol 90:, 494–507. [CrossRef] [PubMed]
    [Google Scholar]
  35. Rai D. , Singh J. K. , Roy N. , Panda D. . ( 2008; ). Curcumin inhibits FtsZ assembly: an attractive mechanism for its antibacterial activity. . Biochem J 410:, 147–155. [CrossRef] [PubMed]
    [Google Scholar]
  36. Rastogi N. , Domadia P. , Shetty S. , Dasgupta D. . ( 2008; ). Screening of natural phenolic compounds for potential to inhibit bacterial cell division protein FtsZ. . Indian J Exp Biol 46:, 783–787.[PubMed]
    [Google Scholar]
  37. Romberg L. , Levin P. A. . ( 2003; ). Assembly dynamics of the bacterial cell division protein FtsZ: poised at the edge of stability. . Annu Rev Microbiol 57:, 125–154. [CrossRef] [PubMed]
    [Google Scholar]
  38. Romberg L. , Simon M. , Erickson H. P. . ( 2001; ). Polymerization of FtsZ, a bacterial homolog of tubulin: is assembly cooperative?. J Biol Chem 276:, 11743–11753. [CrossRef] [PubMed]
    [Google Scholar]
  39. Šali A. , Blundell T. L. . ( 1993; ). Comparative protein modelling by satisfaction of spatial restraints. . J Mol Biol 234:, 779–815. [CrossRef] [PubMed]
    [Google Scholar]
  40. Santra M. K. , Dasgupta D. , Panda D. . ( 2005; ). Deuterium oxide promotes assembly and bundling of FtsZ protofilaments. . Proteins 61:, 1101–1110. [CrossRef] [PubMed]
    [Google Scholar]
  41. Scheffers D.-J. , de Wit J. G. , den Blaauwen T. , Driessen A. J. M. . ( 2002; ). GTP hydrolysis of cell division protein FtsZ: evidence that the active site is formed by the association of monomers. . Biochemistry 41:, 521–529. [CrossRef] [PubMed]
    [Google Scholar]
  42. Schmidt K. L. , Peterson N. D. , Kustusch R. J. , Wissel M. C. , Graham B. , Phillips G. J. , Weiss D. S. . ( 2004; ). A predicted ABC transporter, FtsEX, is needed for cell division in Escherichia coli . . J Bacteriol 186:, 785–793. [CrossRef] [PubMed]
    [Google Scholar]
  43. Sung W. S. , Lee D. G. . ( 2010; ). Antifungal action of chlorogenic acid against pathogenic fungi, mediated by membrane disruption. . Pure Appl Chem 82:, 219–226. [CrossRef]
    [Google Scholar]
  44. Urgaonkar S. , La Pierre H. S. , Meir I. , Lund H. , RayChaudhuri D. , Shaw J. T. . ( 2005; ). Synthesis of antimicrobial natural products targeting FtsZ: (±)-dichamanetin and (±)-2′′′-hydroxy-5′′-benzylisouvarinol-B. . Org Lett 7:, 5609–5612. [CrossRef] [PubMed]
    [Google Scholar]
  45. Walker J. E. , Saraste M. , Runswick M. J. , Gay N. J. . ( 1982; ). Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. . EMBO J 1:, 945–951.[PubMed]
    [Google Scholar]
  46. White E. L. , Suling W. J. , Ross L. J. , Seitz L. E. , Reynolds R. C. . ( 2002; ). 2-Alkoxycarbonylaminopyridines: inhibitors of Mycobacterium tuberculosis FtsZ. . J Antimicrob Chemother 50:, 111–114. [CrossRef] [PubMed]
    [Google Scholar]
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vol. , part 9, pp. 1317–1325

Phenylpropanoid induced filament formation in 168. Interaction of FtsZ of with chlorogenic acid. Contribution plot of hydrophobic interactions. [PDF](134 KB)



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