A synergy interaction of artocarpin and tetracycline against Pseudomonas aeruginosa and its mechanism of action on membrane permeability
Abstract
The emergence of antibacterial resistance has significantly increased. Pseudomonas aeruginosa is associated with nosocomial infection and difficult to control. Artocarpin, a flavonoid from Artocarpus heterophyllus Lam. exhibits several pharmacological properties including antibacterial. The study was performed to evaluate interaction between artocarpin and antibiotics including tetracycline against P. aeruginosa. Its mechanism of action on membrane permeability was also investigated. Broth microdilution was conducted for the susceptibility assay. The interaction of artocarpin and antibiotics was evaluated using checkerboard method, the effect on alteration of membrane cell was investigated using bacteriolysis and the released of 260 nm materials. Artocarpin showed moderate to weak activity against the Gram-negative bacteria including P. aeruginosa with MIC values in the range of 31.25–250 μg/mL. A synergistic effect against P. aeruginosa was produced by the combination of artocarpin (31.25 μg/mL) and tetracycline (1.95 μg/mL) with FICI of 0.37. The time-killing assay showed that artocarpin enhance the antibacterial activity of tetracycline against P. aeruginosa by completely inhibiting the bacterial growth. Additionally, the mixture of artocarpin (31.25 μg/mL) and tetracycline (1.95 μg/mL) disrupted membrane permeability and lead to cell death. These results proposed that the combination of artocarpin and tetracycline may be used to overcome P. aeruginosa infection.
Funding source: Southeast Asia-Europe Joint Funding Scheme
Award Identifier / Grant number: 2020
-
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
-
Research funding: The authors wish to thank Southeast Asia-Europe Joint Funding Scheme for supports.
-
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
References
1. Belo, CG. Antibiotic adjuvants – a strategy to unlock bacterial resistance to antibiotics. Bioorg Med Chem Lett 2017;27:4221–8. https://doi.org/10.1016/j.bmcl.2017.08.027.Search in Google Scholar PubMed
2. Cilloniz, C, Dominedo, C, Torres, A. Multidrug resistant Gram-negative bacteria in community-acquired pneumonia. Crit Care 2019;23. https://doi.org/10.1186/s13054-019-2371-3.Search in Google Scholar PubMed PubMed Central
3. Barbier, F, Andremont, A, Wolff, M, Bouadma, L. Hospital-acquired pneumonia and ventilator-associated pneumonia. Curr Opin Pulm Med 2013;19:216–28. https://doi.org/10.1097/mcp.0b013e32835f27be.Search in Google Scholar
4. Gellatly, SL, Hancock, REW. Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. Pathog Dis 2013;67:159–73. https://doi.org/10.1111/2049-632x.12033.Search in Google Scholar PubMed
5. Lambert, PA. Mechanisms of antibiotic resistance in Pseudomonas aeruginosa. J Roy Soc Med 2002;95:22–6.Search in Google Scholar
6. Breindenstein, EBM, de la Fuente-Nunez, C, Hancock, REW. Pseudomonas aeruginosa: all roads lead to resistance. Trends Microbiol 2011;19:419–26.10.1016/j.tim.2011.04.005Search in Google Scholar PubMed
7. Pang, Z, Raudonis, R, Glick, BR, Lin, TJ, Cheng, Z. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv 2019;37:177–92. https://doi.org/10.1016/j.biotechadv.2018.11.013.Search in Google Scholar PubMed
8. Wagner, H, Ulrich-Merzenich, G. Synergy research: approaching a new generation of phytopharmaceutical. Phytomedicine 2009;16:97–110. https://doi.org/10.1016/j.phymed.2008.12.018.Search in Google Scholar PubMed
9. Cushnie, TTP, Lamb, AJ. Recent advances in understanding the antibacterial properties of flavonoids. Int J Antimicrob Agents 2011;38:99–107. https://doi.org/10.1016/j.ijantimicag.2011.02.014.Search in Google Scholar PubMed
10. Eumkeb, G, Siriwong, S, Thumanu, K. Synergistic activity of luteolin and amoxicillin combination against amoxicillin-resistant Escherichia coli and mode of action. J Photochem Photobiol B Biol 2012;11:247–53. https://doi.org/10.1016/j.jphotobiol.2012.10.006.Search in Google Scholar PubMed
11. Chan, BCL, Ip, M, Gong, H, Lui, SL, See, RH, Jolivalt, C, et al.. Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus (MRSA) RNA4220/pUL5054 and inhibition of MRSA pyruvate kinase. Phytomedicine 2013;2:611–4. https://doi.org/10.1016/j.phymed.2013.02.007.Search in Google Scholar PubMed
12. Lan, JE, Li, XJ, Zhu, XF, Sun, ZL, He, JM, Zloh, M, et al.. Flavonoids from Artemisia rupestris and their synergistic antibacterial effects on drug-resistant Staphylococcus aureus. Nat Prod Res 2021;35:1881–6. 10.1080/14786419.2019.1639182.10.1080/14786419.2019.1639182Search in Google Scholar PubMed
13. Arung, ET, Yoshikawa, K, Shimizu, K, Kondo, R. Isoprenoid-substituted from wood of Artocarpus heterophyllus on B16 melanoma cells: cytotoxicity and structural criteria. Fitoterapia 2010;81:120–3. https://doi.org/10.1016/j.fitote.2009.08.001.Search in Google Scholar PubMed
14. Septama, AW, Panichayupakaranant, P. Antibacterial assay-guided isolation of antibacterial compounds from Artocarpus heterophyllus heartwoods. Pharm Biol 2015;53:1608–13. https://doi.org/10.3109/13880209.2014.996819.Search in Google Scholar PubMed
15. Septama, AW, Jantan, I, Panichayupakaranant, P. Flavonoids of Artocarpus heterophyllus Lam. heartwood inhibit the innate immune responses of human phagocytes. J Pharm Pharmacol 2018;70:1242–52. https://doi.org/10.1111/jphp.12952.Search in Google Scholar PubMed
16. Shim, JH. Anti-aging effect of artocarpin in UVA-irradiated normal human epidermal keratinocytes. Korean J Pharmacogn 2020;51:49–54.Search in Google Scholar
17. Septama, AW, Panichayupakaranant, P. Synergistic effect of artocarpin on antibacterial activity of some antibiotics against methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Pharm Biol 2016;54:686–91. https://doi.org/10.3109/13880209.2015.1072566.Search in Google Scholar PubMed
18. NCCLS (National Committee for Clinical Laboratory Standard). Performance standard for antimicrobial susceptibility testing. Pennsylvania, USA: Ninth informational supplement; 2008.Search in Google Scholar
19. Milne, KE, Gould, IM. Combination antimicrobial susceptibility testing of multidrug-resistant Stenotrophomonas maltophilia from cystic fibrosis patients. Antimicrob Agents Chemother 2012;56:4071–7. https://doi.org/10.1128/aac.00072-12.Search in Google Scholar
20. Hamoud, R, Zimmermann, S, Reichling, J, Wink, M. Synergistic interaction in two-drug and three-drug combinations (thymol, EDTA and vancomycin) against multi drug resistant bacteria including E. coli. Phytomedicine 2014;21:443–7. https://doi.org/10.1016/j.phymed.2013.10.016.Search in Google Scholar PubMed
21. Septama, AW, Xiao, J, Panichayupakaranant, P. A synergistic effect of artocarpanone from Artocarpus heterophyllus L. (Moraceae) on the antibacterial activity of selected antibiotics and cell membrane permeability. J Intercult Ethnopharmacol 2017;6:186–91. https://doi.org/10.5455/jice.20170327073745.Search in Google Scholar PubMed PubMed Central
22. Reygaert, WC. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiol 2018;4:482–501. https://doi.org/10.3934/microbiol.2018.3.482.Search in Google Scholar PubMed PubMed Central
23. Karaiskos, I, Giamarellou, H. Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches. Expet Opin Pharmacother 2014;15:1351–70. https://doi.org/10.1517/14656566.2014.914172.Search in Google Scholar PubMed PubMed Central
24. Yang, Y, Zhang, Z, Li, S, Ye, X, Li, X, He, K. Synergy effects of herb extracts: pharmacokinetics and pharmacodynamics basis. Fitoterapia 2014;92:133–47. https://doi.org/10.1016/j.fitote.2013.10.010.Search in Google Scholar PubMed
25. Horne, JE, Brockwell, DJ, Radford, SE. Role of the lipid bilayer in outer membrane protein folding in Gram-negative bacteria. J Biol Chem 2020;295:10340–67. https://doi.org/10.1074/jbc.rev120.011473.Search in Google Scholar
26. Lam, AK, Panlilio, H, Pusavat, J, Wouters, CL, Moen, EL, Rice, CV. Overcoming multidrug resistance and biofilms of Pseudomonas aeruginosa with a single dual-function potentiator of β-lactams. ACS Infect Dis 2020;6:1085–97. https://doi.org/10.1021/acsinfecdis.9b00486.Search in Google Scholar PubMed PubMed Central
27. Devi, KP, Nisha, SA, Sakthivel, R, Pandian, SK. Eugenol (an essential oil of clove) acts as an antibacterial agent agiants Salmonella typhi by disturbing the cellular membrane. J Ethnopharmacol 2020;130:107–15.10.1016/j.jep.2010.04.025Search in Google Scholar PubMed
28. Panichayupakaranant, P, Septama, AW, Sinviratpong, A. Synergistic activity of lawsone methyl ether in combination with some antibiotics and artocarpin against methicillin-resistant Staphylococcus aureus, Candida albicans, and Trychophyton rubrum. Chin Herb Med 2019;11:321–5. https://doi.org/10.1016/j.chmed.2019.06.001.Search in Google Scholar
29. Hendrich, AB. Flavonoid-membrane interactions: possible consequences for biological effects of some polyphenolic compounds. Act Pharmacol Sin 2006;27:27–40. https://doi.org/10.1111/j.1745-7254.2006.00238.x.Search in Google Scholar PubMed
30. Yao, X, Zhu, X, Pan, S, Fang, Y, Jiang, F, Philips, GO, et al.. Antimicrobial activity of nobiletin and tangeretin against Pseudomonas aeruginosa. Food Chem 2012;132:1883–90. https://doi.org/10.1016/j.foodchem.2011.12.021.Search in Google Scholar
31. Septama, AW, Panichayupakaranant, P. Antibacterial activity of artocarpanone isolated from Artocarpus heterophyllus heartwoods against diarrheal pathogens and its mechanism of action on membrane permeability. J Appl Pharmaceut Sci 2017;7:64–8.Search in Google Scholar
32. Chopra, I, Roberts, M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 2001;65:232–60. https://doi.org/10.1128/mmbr.65.2.232-260.2001.Search in Google Scholar PubMed PubMed Central
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Research Articles
- Isolation and characterization of chemical constituents from Chaerophyllum bulbosum roots and their enzyme inhibitory and antioxidant effects
- Monascin and monascinol, azaphilonoid pigments from Mortierella polycephala AM1: in silico and in vitro targeting of the angiogenic VEGFR2 kinase
- Novel Ag(I)-NHC complex: synthesis, in vitro cytotoxic activity, molecular docking, and quantum chemical studies
- NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement
- Oxidative stress and cyto-genotoxicity induced by poly-d-glucosamine in human blood cells in vitro
- A synergy interaction of artocarpin and tetracycline against Pseudomonas aeruginosa and its mechanism of action on membrane permeability
- Review Articles
- Cytokine storm syndrome in SARS-CoV-2: a review
- A comprehensive review on the development of probiotic supplemented confectioneries
Articles in the same Issue
- Frontmatter
- Research Articles
- Isolation and characterization of chemical constituents from Chaerophyllum bulbosum roots and their enzyme inhibitory and antioxidant effects
- Monascin and monascinol, azaphilonoid pigments from Mortierella polycephala AM1: in silico and in vitro targeting of the angiogenic VEGFR2 kinase
- Novel Ag(I)-NHC complex: synthesis, in vitro cytotoxic activity, molecular docking, and quantum chemical studies
- NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement
- Oxidative stress and cyto-genotoxicity induced by poly-d-glucosamine in human blood cells in vitro
- A synergy interaction of artocarpin and tetracycline against Pseudomonas aeruginosa and its mechanism of action on membrane permeability
- Review Articles
- Cytokine storm syndrome in SARS-CoV-2: a review
- A comprehensive review on the development of probiotic supplemented confectioneries