In Vitro Evaluation of Anticancer Drugs as Antimicrobial Agent against the Pathogenic Enteric Bacteria
Keywords:
Anticancer Drugs, Drug Repurposing, Efflux Pump Inhibitor, Multidrug Resistance, Salmonella TyphiAbstract
Drug repurposing and drug combination have been suggested as a major strategy to counter the spread of
antimicrobial resistance in clinical and community settings. Drug repurposing explores the potential of existing
drugs for new indications with respect to human disease. Mainstream anticancer drug paclitaxel and vinblastine
were tested as potential efflux pump inhibitors in in vitro assays. Both the anticancer drugs failed to produce
zone of inhibition on MHA plates inoculated with Salmonella Typhi in disk diffusion testing. MIC obtained for
the two drugs were found as 80μg/ml (Paclitaxel) and 160 μg/ml (vinblastine) respectively. When tested for
synergy with kanamycin and ciprofloxacin, paclitaxel and vinblastine resulted in indifference (FICI value =1 for
both the antibiotics). The combination of anticancer and antibiotic drugs showed bacteriostatic nature in the
absence of 3log10 reduction in viable Salmonella CFUs over 24 hrs time period in time kill assay. Whereas the
marginal activity was observed in EtBr cartwheel assay as compared to control. Thus in vitro studies paclitaxel
and vinblastine cannot be repurposed as antimicrobial against Salmonella Typhi.
Downloads
References
Ahburn, T. T., & Thor, K. B. (2004). Drug repositioning identifying and developing new uses for existing drug.
Nature Review Drug Discovery, 3(8), 673-683.
Aygul, A. (2015). The importance of efflux systems in antibiotic resistance and efflux pump inhibitors in the
management of resistance. Mikrobiyoloji Bulteni, 49 (2), 278-291.
Bonev, B., Hooper, J., & Parisot, J. (2008). Principles of assessing bacterial susceptibility to antibiotics using the
agar diffusion method. Journal of Antimicrobial Chemotherapy, 61 (6), 1295-1301.
Chowdhury, R., Bakshi, R., Wang, J., Yildirir, G., Liu, B., Pappas-Brown, V., Tolun, G., Griffith, J. D., Shapiro,
T. A., Jensen, R. E., & Englund, P. T. (2010). The killing of African trypanosomes by ethidium bromide. PLoS
Pathogens, 6 (12), e1001226.
Patel, J. B., Cockerill, F. R., Nicolau, D. P., Bradford, P. A., Powell, M., Eliopoulos, G. M., Miller, L. A., Hindler,
J. A., Swenson, J. M., Jenkins, S. G., Traczewski, M. M., Lewis, J. S., Turnidge, J. D., Limbago, B., Weinstein,
M. P., & Zimmer, B. L. (2015). CLSI performance standards for antimicrobial disk susceptibility tests; approved
standard twelfth edition. CLSI document M02-A12, 35(1), 1-15. Wayne, P. A.: Clinical and Laboratory Standards
Institute.
Fernando, D. M., & Kumar, A. (2013). Resistance-nodulation-division multidrug efflux pumps in gram-negative
bacteria: role in virulence. Antibiotics, 2(1), 163-181.
Journal of Graphic Era University
Vol. 5, Issue 2, 155-163, 2017
ISSN: 0975-1416 (Print), 2456-4281 (Online)
Garvey, M. I., & Piddock, L. J. V. (2008). The efflux pump inhibitor reserpine selects multidrug-resistant
streptococcus pneumoniae strains that over express the ABC transporters PatA and PatB, Antimicrobial Agents
and Chemotherapy, 52 (2), 1677-1685.
Gould, M., & Bal, A. M. (2013). New antibiotic agents in the pipeline and how they can help overcome
microbial resistance. Virulence, 4(2), 185-191.
Gupta, P., Gautam, P. & Rai, N. (2015). Anticancer drugs as potential inhibitors of AcrAB-TolC of multidrug
resistant Escherichia coli: an in silico molecular modeling and docking study. Asian Journal of Pharmaceutical and
Clinical Research, 8 (1), 351-358.
Huttner, A., Harbarth, S., Carlet, J., Cosgrove, S., Goossens, H., Holmes, A., Jarlier, V., Voss, A. & Pittet, D.
(2013). Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum.
Antimicrobial Resistance and Infection Control, 2(31), 2047-2994.
Kalle, A. M., & Rizvi, A. (2011). Inhibition of bacterial multidrug resistance by celecoxib, a cyclooxygenase-2
inhibitor. Antimicrobial Agents and Chemotherapy, 55(1), 439-442.
Lehar, J., Krueger, A. S., Avery, W., Heilbut, A. M., Johansen, L. M., Price, E. R., Rickles, R. J., Short III, G. F.,
Staunton, J. E., Jin, X., Lee, M. S., Zimmermann, G. R., & Borisy A. A. (2009). Synergistic drug combinations
tend to improve therapeutically relevant selectivity. Nature Biotechnology, 27(7), 659-666.
Li, X. Z., & Nikaido, H. (2004). Efflux mediated drug resistance in bacteria. Drugs, 64 (2), 159-204.
Lomovskaya, O., & Watkins, W. (2001). Inhibition of efflux pumps as a novel approach to combat drug resistance
in bacteria. Journal of Molecular and Microbiology Biotechnology, 3(2), 225-236.
Martins, M., McCusker, M. P., Viveiros, M., Couto, I., Fanning, S., Pages, J. M., & Amaral, L. (2013). A simple
method for assessment of MDR bacteria for over-expressed efflux pumps. Open Microbiology, 7(1), 72-82.
Nikaido, E., Giraud, E., Baucheron, S., Yamasaki, S., Wiedemann, A., Okamoto, K., Takagi, T., Yamaguchi, A.,
Cloeckaert, A., & Nishino, K. (2012). Effects of indole on drug resistance and virulence of Salmonella enterica
serovar Typhimurium revealed by genome-wide analyses. Gut Pathogen, 4 (1), 2-13.
Olajuyigbe, O. O., & Afolayan, A. J. (2012). In vitro antibacterial and time-kill evaluation of the Erythrina caffra
Thunb. Extract against bacteria associated with diarrhoea. Scientific World Journal, 738314, 2012, 1-8.
Oprea, T. I., & Mestres, J. (2012). Drug repurposing: far beyond new targets for old drugs, American
Association of Pharmaceutical Sciences, 14(4), 759-763.
Piddock, L. J. V. (2006). Multidrug resistance efflux pumps not just for resistance. Nature Reviews
Microbiology, 4(8), 629-635.
Piddock, L. J., Garvey, M. I., Rahman, M. M., & Gibbons, S. (2010). Natural and synthetic compounds such as
trimethoprim behave as inhibitors of efflux in Gram-negative bacteria. Journal of Antimicrobial Chemotherapy, 65
(6), 1215-1223.
Reller, L. B., Weinstein, M., Jorgensen, J. H., & Ferraro, M. J. (2009). Antimicrobial susceptibility testing: a
review of general principles and contemporary practices. Clinical Infectious Disease, 49 (11), 1749-1755.
Rowe, B., Ward, L. R., & Threlfall, E. J. (1997). Multidrug-resistant Salmonella typhi: a worldwide epidemic.
Clinical Infectious Disease, 24 (1), 106-109.
Shah, Z., Mahbuba, R., & Turcotte, B. (2013). The anticancer drug tirapazamine has antimicrobial activity
against Escherichia coli, Staphylococcus aureus and Clostridium difficile. FEMS Microbiology Letters, 347(1),
-69.
Journal of Graphic Era University
Vol. 5, Issue 2, 155-163, 2017
ISSN: 0975-1416 (Print), 2456-4281 (Online)
Sopirala, M. M., Mangino, J. E., Gebreyes, W. A., Biller, B., Bannerman, T., Balada-Llasat, J. M., & Pancholi, P.
(2010). Synergy testing by Etest, microdilution checker board, and time-kill methods for pan-drug-resistant
Acinetobacter baumannii. Antimicrobial Agents Chemotherapy, 54 (11), 4678-4683
