REVERSION OF ANTIBIOTIC RESISTANCE WITH BETA-LACTAMASE INHIBITOR FROM MEDICINAL PLANTS
Â Objective: Screening of medicinal plants for the presence of beta-lactamase inhibitor identified three plants; Terminalia chebula, Terminalia bellirica, and Ocimum tenuiflorum, extracts of which inhibit beta-lactamase enzyme in vitro. The objective of this study was to evaluate and compare beta-lactamase inhibiting potential of these plant extracts.
Methods: Extracts of these plants were prepared with 6 solvents of different polarity. Beta-lactamase inhibition study was performed using antibiotic-resistant bacteria in bioassay and by micro-iodometric assay. Multidrug-resistant clinical strains of Escherichia coli and laboratory strain with plasmid carrying beta-lactamase gene as positive control were used.
Results: Our results from bioassay, as well as micro-iodometric assay for enzyme activity, confirmed the presence of beta-lactamase inhibitor in these plant extracts. Among the extracts made by different solvents, hexane and ethyl acetate extract of T. chebula, hexane extract of T. bellirica, and all extracts of O. tenuiflorum except dichloromethane, possessed beta-lactamase inhibitor. Multidrug-resistant clinical isolate of E. coli AIIMS-1 could be reverted by applying 50 Î¼g/Î¼l of extract of all the medicinal plants. The micro-iodometric result showed highest beta-lactamase inhibition with O. tenuiflorum extracts. Comparative evaluation of the O. tenuiflorum extracts with increasing concentration of inhibitor suggests that ethyl acetate extract of O. tenuiflorum contains the highest inhibition potential, which is comparable with clavulanic acid.
Conclusion: The results demonstrated that the ethyl acetate extract of O. tenuiflorum contain the highest level of beta-lactamase inhibitor, which in the future can be used as an alternative to synthetic beta-lactamase inhibitors that are presently being used to control beta-lactam antibiotic resistance
2. Wilke MS, Lovering AL, Strynadka NC. Beta-lactam antibiotic resistance: A current structural perspective. Curr Opin Microbiol 2005;8(5):525-33.
3. Sobel JD, Kaye D. Mandell, Douglas and Bennettâ€™s. Principals and practice of infectious diseases. In: Mandell GL, Bennett JE, Dolin R, editors. Urinary Tract Infections. 5th ed. Philadelphia, PA, London: Churchill Livingstone; 2000. p. 3386.
4. Srinivas V. Treatment of recurrent acute cystitis with sulbactomax: A case report. Int J Int J Pharm Pharm Sci 2012;1(4):560-1.
5. Landgren M, OdÃ©n H, KÃ¼hn I, Osterlund A, Kahlmeter G. Diversity among 2481 Escherichia coli from women with community-acquired lower urinary tract infections in 17 countries. J Antimicrob Chemother 2005;55(6):928-37.
6. Allen UD, MacDonald N, Fuite L, Chan F, Stephens D. Risk factors for resistance to â€œfirst-lineâ€ antimicrobials among urinary tract isolates of Escherichia coli in children. CMAJ 1999;160(10):1436-40.
7. Rupp ME, Fey PD. Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae: Considerations for diagnosis, prevention and drug treatment. Drugs 2003;63(4):353-65.
8. Devi AS, Rajkumar J. A study on antibiotic susceptibility and resistance profiles of bacterial strains isolated from patients with urinary tract infection (UTI) at Kanchipuram district, Tamilnadu, India. Int J Pharm Pharm Sci 2013;3(5):817-20.
9. Whoâ€™s Certified. Global Priority List of Antibiotic-Resistant Bacteria
to Guide Research, Discovery, and Development of New Antibiotics; 2017. Available from: http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf?ua=1. [Last cited on 2017 Feb 27].
10. Livermore DM. Beta-lactamases in laboratory and clinical resistance. Clin Microbiol Rev 1995;8(4):557-84.
11. Rawat D, Nair D. Extended-spectrum ÃŸ-lactamases in Gram Negative Bacteria. J Glob Infect Dis 2010;2(3):263-74.
12. Drawz SM, Bonomo RA. Three decades of beta-lactamase inhibitors. Clin Microbiol Rev 2010;23(1):160-201.
13. Mehrotra S, Srivastava AK, Nandi SP. Comparative antimicrobial activities of Neem, amla, aloe, Assam tea and clove extracts against Vibrio cholerae, Staphylococcus aureus and Pseudomonas aeruginosa. J Med Plants Res 2010;4(18):2473-8.
14. Mugnier P, Dubrous P, Casin I, Arlet G, Collatz E. A TEM-derived extended-spectrum beta-lactamase in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1996;40(11):2488-93.
15. Catlin BW. Iodometric detection of Haemophilus influenzae beta-lactamase: Rapid presumptive test for ampicillin resistance. Antimicrob Agents Chemother 1975;7(3):265-70.
16. Madhavan HN, Murali S. Mechanisms of development of antibiotic resistance in bacteria among clinical specimens. J Clin Biomed Sci 2011;1(2):42-8.
17. Anjum F, Kadri SM, Ahmad I, Ahmad S. Study of recurrent urinary tract infections among woman attending outpatient department in S.M.H.S. hospital. JK Pract 2004;11(4):272-3.
18. Karlowsky JA, Kelly LJ, Thornsberry C, Jones ME, Sahm DF. Trends in antimicrobial resistance among urinary tract infection isolates of Escherichia coli from female outpatients in the United States. Antimicrob Agents Chemother 2002;46(8):2540-5.
19. Sabath LD, Elder HA, McCall CE, Finland M. Synergistic combinations of penicillins in the treatment of bacteriuria. N Engl J Med 1967;277(5):232-8.
20. Rubens DM, Constantin OO, Moevi AA, Nathalie GK, Daouda T, David NJ, et al. Anti-Staphylococcus aureus activity of the aqueous extract and hexanic fraction of Thonningia sanguinea (Cote Ivoire). Int J Pharmacogn Phytochem Res 2015;7(2):301-6.
21. Ahmad I, Aqil F. In vitro efficacy of bioactive extracts of 15 medicinal plants against ESbL-producing multidrug-resistant enteric bacteria. Microbiol Res 2007;162(3):264-75.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.