Advertisement

In vitro efficacy of diclofenac against Listeria monocytogenes

  • N. K. Dutta
  • K. Mazumdar
  • M. W. Baek
  • D. J. Kim
  • Y. R. Na
  • S. H. Park
  • H. K. Lee
  • B. H. Lee
  • J. H. Park
Concise Article

Abstract

Chemotherapy is often futile in systemic listeriosis, translating to being a peril to public health. There is, thus, an imperative need for novel antilisterial compounds, possibly acting through mechanisms dissimilar to those of existing drugs. The present study describes one such agent—the non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium (Dc). The National Committee for Clinical Laboratory Standards (NCCLS) minimum inhibitory concentration (MIC), mode of action, and two mechanisms of action, i.e., on bacterial DNA and membrane, have been characterized with respect to Dc. The drug showed noteworthy inhibitory action (MIC90 = 50 μg/ml) against Listeria strains, demonstrated cidal (minimum bactericidal concentration [MBC]=100 μg/ml) activity, inhibited listerial DNA synthesis (45.48%; incorporation of [methyl-3H] thymidine), and possessed bacterial membrane-damaging activity (37.33%; BacLight assay). Dc could be used as a lead compound for the synthesis of new, more active agents perhaps devoid of side effects. Further, quantitative structure–activity relationship (QSAR) studies will contribute to a new generation of promising adjuvants to existing antilisterial drugs.

Keywords

Minimum Inhibitory Concentration Blood Stream Infection Listeriosis Agar Dilution Method Antilisterial Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by grants provided by the Korea Research Foundation and the Brain Korea 21 project, South Korea.

Transparency declarations: none to declare.

References

  1. 1.
    Gillespie IA, McLauchlin J, Grant KA, Little CL, Mithani V, Penman C, Lane C, Regan M (2006) Changing pattern of human listeriosis, England and Wales, 2001–2004. Emerg Infect Dis 12(9):1361–1366PubMedGoogle Scholar
  2. 2.
    Kristiansen JE (1991) Antimicrobial activity of non-antibiotics. ASM News 57(3):135–139Google Scholar
  3. 3.
    Dutta NK, Annadurai S, Mazumdar K, Dastidar SG, Kristiansen JE, Molnar J, Martins M, Amaral L (2007) Potential management of resistant microbial infections with a novel non-antibiotic: the anti-inflammatory drug diclofenac sodium. Int J Antimicrob Agents 30(3):242–249PubMedCrossRefGoogle Scholar
  4. 4.
    Nelson KE, Fouts DE, Mongodin EF, Ravel J, DeBoy RT, Kolonay JF, Rasko DA, Angiuoli SV, Gill SR, Paulsen IT, Peterson J, White O, Nelson WC, Nierman W, Beanan MJ, Brinkac LM, Daugherty SC, Dodson RJ, Durkin AS, Madupu R, Haft DH, Selengut J, Van Aken S, Khouri H, Fedorova N, Forberger H, Tran B, Kathariou S, Wonderling LD, Uhlich GA, Bayles DO, Luchansky JB, Fraser CM (2004) Whole genome comparisons of serotype 4b and 1/2a strains of the food-borne pathogen Listeria monocytogenes reveal new insights into the core genome components of this species. Nucleic Acids Res 32(8):2386–2395PubMedCrossRefGoogle Scholar
  5. 5.
    Washington JA 2nd, Sutter VL (1980) Dilution susceptibility test: agar and macro-broth dilution procedures. In: Lennette EH, Balows A, Hausler WJ, Truant JP (eds) Manual of clinical microbiology, 3rd ed. American Society for Microbiology, Washington, DC, pp 453–458Google Scholar
  6. 6.
    National Committee for Clinical Laboratory Standards (NCCLS) (2003) Methods for dilution in antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard M7-A6 and MIC testing supplemental tables M100-S13, 6th edn, vol 23, no 2. NCCLS, Wayne, PAGoogle Scholar
  7. 7.
    Krogstad DJ, Moellering RC (1980) Combinations of antibiotics, mechanisms of interaction against bacteria. In: Lorian V (ed), Antibiotics in laboratory medicine. Lippincott Williams & Wilkins, Baltimore, London, p 305Google Scholar
  8. 8.
    Robards AW, Wilson AJ (1993) Basic biological preparation techniques for TEM. In: Procedures in electron microscopy. Wiley, Chichester, United Kingdom, p 84Google Scholar
  9. 9.
    Lemaire S, Van Bambeke F, Mingeot-Leclercq M-P, Tulkens PM (2005) Activity of three β-lactams (ertapenem, meropenem and ampicillin) against intraphagocytic Listeria monocytogenes and Staphylococcus aureus. J Antimicrob Chemother 55:897–904PubMedCrossRefGoogle Scholar
  10. 10.
    Hilliard JJ, Goldschmidt RM, Licata L, Baum EZ, Bush K (1999) Multiple mechanisms of action for inhibitors of histidine protein kinases from bacterial two-component systems. Antimicrob Agents Chemother 43(7):1693–1699PubMedGoogle Scholar
  11. 11.
    Wilson JM, Oliva B, Cassels R, O’Hanlon PJ, Chopra I (1995) SB 205952, a novel semisynthetic monic acid analog with at least two modes of action. Antimicrob Agents Chemother 39(9):1925–1933PubMedGoogle Scholar
  12. 12.
    Swaminathan B, Gerner-Smidt P (2007) The epidemiology of human listeriosis. Microbes Infect 9:1236–1243PubMedCrossRefGoogle Scholar
  13. 13.
    Muñoz-Criado S, Muñoz-Bellido JL, García-Rodríguez JA (1996) In vitro activity of nonsteroidal anti-inflammatory agents, phenotiazines, and antidepressants against Brucella species. Euro J Clinic Microb Infect Dis 15(5):418–420CrossRefGoogle Scholar
  14. 14.
    Mazumdar K, Dutta NK, Dastidar SG, Motohashi N, Shirataki Y (2006) Diclofenac in the management of E. coli urinary tract infections. In Vivo 20(5):613–619PubMedGoogle Scholar
  15. 15.
    Dutta NK, Mazumdar K, Dastidar SG, Park JH (2007) Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice. Int J Antimicrob Agents 30(4):336–340PubMedCrossRefGoogle Scholar
  16. 16.
    Theodorou A, Demertzis MA, Kovala-Demertzi D, Lioliou EE, Pantazaki AA, Kyriakidis DA (1999) Copper(II) complexes of diclofenac: spectroscopic studies and DNA strand breakage. BioMetals 12(2):167–172CrossRefGoogle Scholar
  17. 17.
    Amaral L, Viveiros M, Kristiansen JE (2006) “Non-antibiotics”: alternative therapy for the management of MDRTB and MRSA in economically disadvantaged countries. Curr Drug Targets 7(7):887–891PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • N. K. Dutta
    • 1
  • K. Mazumdar
    • 2
  • M. W. Baek
    • 1
  • D. J. Kim
    • 1
  • Y. R. Na
    • 1
  • S. H. Park
    • 1
  • H. K. Lee
    • 1
  • B. H. Lee
    • 3
  • J. H. Park
    • 1
  1. 1.Institute of Laboratory Animal Resources, Laboratory Animal MedicineCollege of Veterinary Medicine and KRF Zoonotic Disease Priority Research Institute, Seoul National UniversitySeoulSouth Korea
  2. 2.Department of Microbiology and ImmunologyCollege of Medicine, Seoul National UniversitySeoulSouth Korea
  3. 3.Department of Animal ExperimentationCollege of Medicine, Seoul National UniversitySeoulSouth Korea

Personalised recommendations