Antibacterial activity of endosymbiotic bacterial compound from Pheretima sp. earthworms inhibit the growth of Salmonella Typhi and Staphylococcus aureus: in vitro and in silico approach
,
Abstract
Background and Objectives: Earthworms coexist with various pathogenic microorganisms; thus, their immunity mechanisms have developed through a long process of adaptation, including through endogenous bacterial symbionts. This study aims to identify earthworm endosymbiont bacteria compounds and their antibacterial activity through an in vitro approach supported by an in silico approach.
Materials and Methods: This research was conducted using the in vitro inhibition test through agar diffusion and the in silico test using molecular docking applications, namely, PyRx and Way2Drugs Prediction of Activity Spectra for Substances (PASS).
Results: The in vitro results showed a potent inhibition activity with a clear zone diameter of 21.75 and 15.5 mm for Staphylococcus aureus and Salmonella Typhi, respectively. These results are supported by chromatography and in silico tests, which showed that several compounds in endosymbiotic bacteria, cyclo (phenylalanyl-prolyl) and sedanolide, have high binding affinity values with several antibiotic-related target proteins in both pathogenic bacteria. Cyclo (phenylalanyl-prolyl) has the highest binding affinity of -6.0 to dihydropteroate synthase, -8.2 to topoisomerase, and -8.2 to the outer membrane, whereas sedanolide has the highest binding affinity to DNA gyrase with approximately -7.3. This antibiotic activity was also clarified through the Way2Drugs PASS application.
Conclusion: Ten active compounds of endosymbiont bacteria, Cyclo (phenylalanyl-prolyl) and sedanolide were potential candidates for antibacterial compounds based on the inhibition test of the agar diffusion method and the results of reverse docking and Way2Drugs PASS.
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29. Ołdak A, Zielińska D, Rzepkowska A, Kołożyn-Krajewska D. Comparison of antibacterial activity of Lactobacillus plantarum strains isolated from two different kinds of regional cheeses from Poland: Oscypek and Korycinski cheese. Biomed Res Int 2017;2017:6820369.
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31. Ocampo PS, Lazar V, Papp B, Arnoldini M, Abel Zur Wiesch P, Busa-Fekete R, et al. Antagonism between bacteriostatic and bactericidal antibiotics is prevalent. Antimicrob Agents Chemother 2014;58:4573-4582.
32. Nemeth J, Oesch G, Kuster SP. Bacteriostatic versus bactericidal antibiotics for patients with serious bacterial infections: systematic review and meta-analysis. J Antimicrob Chemother 2015;70:382-395.
33. Soares GM, Figueiredo LC, Faveri M, Cortelli SC, Duarte PM, Feres M. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs. J Appl Oral Sci 2012;20:295-309.
34. Ramachandran R, Chalasani AG, Lal R, Roy U. A broad-spectrum antimicrobial activity of Bacillus subtilis RLID 12.1. ScientificWorldJournal 2014;2014:968487.
35. Breijyeh Z, Jubeh B, Karaman R. Resistance of gram-negative bacteria to current antibacterial agents and approaches to resolve it. Molecules 2020;25:1340.
36. Kırmusaoğlu S, Gareayaghi N, Kocazeybek BS (2019). Introductory chapter : the action mechanisms of antibiotics and antibiotic resistance. In: Antimicrobials, antibiotic resistance, antibiofilm strategies and activity methods. Intechopen, 1st ed. London, UK, pp.1-9.
37. Eyler RF, Shvets K. Clinical pharmacology of antibiotics. Clin J Am Soc Nephrol 2019;14:1080-1090.
38. El-Attar MAZ, Elbayaa RY, Shaaban OG, Habib NS, Abdel Wahab AE, Abdelwahab IA, et al. Design, synthesis, antibacterial evaluation and molecular docking studies of some new quinoxaline derivatives targeting dihyropteroate synthase enzyme. Bioorg Chem 2018;76:437-448.
39. Ferreira LG, Dos Santos RN, Oliva G, Andricopulo AD. Molecular docking and structure-based drug design strategies. Molecules 2015;20:13384-13421.
40. Masters PA, O’Bryan TA, Zurlo J, Miller DQ, Joshi N. Trimethoprim-sulfamethoxazole revisited. Arch Intern Med 2003;163:402-410.
41. Kordus SL, Baughn AD. Revitalizing antifolates through understanding mechanisms that govern susceptibility and resistance. Medchemcomm 2019;10:880-895.
42. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochemistry 2014;53:1565-1574.
43. Öztürk H, Ozkirimli E, Özgür A. Classification of beta-lactamases and penicillin binding proteins using ligand centric network models. PLoS One 2015;10(2):e0117874.
2. Rosenblatt-Farrell N. The landscape of antibiotic resistance. Environ Health Perspect 2009;117:A244-250.
3. World Health Organization (WHO). Antimicrobial resistance: global report on surveillance 2014.
4. Khameneh B, Iranshahy M, Soheili V, Fazzly Bazzaz BS. Review on plant antimicrobials: a mechanistic viewpoint. Antimicrob Resist Infect Control 2019;8:118.
5. Elisha IL, Botha FS, McGaw LJ, Eloff JN. The antibacterial activity of extracts of nine plant species with good activity against Escherichia coli against five other bacteria and cytotoxicity of extracts. BMC Complement Altern Med 2017;17:133.
6. Mambe FT, Na-Iya J, Fotso GW, Ashu F, Ngameni B, Ngadjui BT, et al. Antibacterial and antibiotic modifying potential of crude extracts, fractions, and compounds from Acacia polyacantha willd. against MDR gram-negative bacteria. Evid Based Complement Alternat Med 2019;2019:7507549.
7. Bereksi MS, Hassaine H, Bekhechi C, Abdelouahid DE. Evaluation of antibacterial activity of some medicinal plants extracts commonly used in Algerian traditional medicine against some pathogenic bacteria. Pharmacogn J 2018;10:507-512.
8. Shen Y. Earthworms in traditional Chinese medicine) Oligochaeta: Lumbricidae, Megascolecidae) Zoology in the Middle East 2010;51(suppl 2) :171-173.
9. Dharmawati IGAA, Mahadewa TGB, Widyadharma IPE. Antibacterial activity of Lumbricus rubellus earthworm extract against Porphyromonas gingivalis as the bacterial cause of periodontitis. Open Access Maced J Med Sci 2019;7:1032-1036.
10. Gil SV, Gil JRV. Sustainable management of agricultural systems: physical and biological aspects of soil health. Elsevier 2011;297-301.
11. Byzov BA, Nechitailo TIu, Bumazhkin BK, Kurakov AV, Golyshin PN, Zviagintsev DG. [Microorganisms from the digestive tract of the earthworms]. Mikrobiologiia 2009;78:404-413.
12. Amr AEE, Abo-Ghalia MH, Moustafa GO, Al-Omar MA, Nossier ES, Elsayed EA. Design, synthesis and docking studies of novel macrocyclic pentapeptides as anticancer multi-targeted kinase inhibitors. Molecules 2018;23:2416.
13. Jamkhande PG, Pathan SK, Wadher SJ. In silico PASS analysis and determination of antimycobacterial, antifungal, and antioxidant efficacies of maslinic acid in an extract rich in pentacyclic triterpenoids. Int J Mycobacteriol 2016;5:417-425.
14. Ginovyan M, Keryan A, Bazukyan I, Ghazaryan P, Trchounian, A. The large scale antibacterial, antifungal and anti-phage efficiency of Petamcin-A: new multicomponent preparation for skin diseases treatment. Ann Clin Microbiol Antimicrob 2015;14:28.
15. Rahman NA, Chowdhury AJK, Abidin ZAZ. Antibiotic resistant bacteria from sediment of coastal water of Pahang, Malaysia. J Teknologi 2015;77:65-70.
16. Hassan AS, Askar AA, Nossier ES, Naglah AM, Moustafa GO, Al-Omar MA. Antibacterial evaluation, in silico characters and molecular docking of schiff bases derived from 5-aminopyrazoles. Molecules 2019;24:3130.
17. Adnan M, Nazim Uddin Chy M, Mostafa Kamal ATM, Azad MOK, Paul A, Uddin SB, et al. Investigation of the biological activities and characterization of bioactive constituents of Ophiorrhiza rugosa var. prostrata (D.Don) & Mondal leaves through in vivo, in vitro, and in silico approaches. Molecules 2019;24:1367.
18. Khan ZA, Siddiqui MF, Park S. Current and emerging methods of antibiotic susceptibility testing. Diagnostics (Basel) 2019;9:49.
19. Parry CM, Thuy CT, Dongol S, Karkey A, Vinh H, Chinh NT, et al. Suitable disk antimicrobial susceptibility breakpoints defining Salmonella enterica serovar Typhi isolates with reduced susceptibility to fluoroquinolones. Antimicrob Agents Chemother 2010;54:5201-5208.
20. Dougan G, Baker S. Salmonella enterica serovar Typhi and the pathogenesis of typhoid fever. Annu Rev Microbiol 2014;68:317-336.
21. Crump JA. Progress in typhoid fever epidemiology. Clin Infect Dis 2019;68(Suppl 1):S4-S9.
22. World Health Organization (WHO). Immunization, vaccines and biologicals typhoid; 2019.
23. Lu T, Deleo FR (2016). Pathogenesis of Staphylococcus aureus in Humans. In: Human emerging and re-emerging infection and parasitic infection. John Wiley & Sons, Inc, 1st ed. USA: Hamilton, MT, National Institutes of Health, pp. 711-748.
24. DeLeo FR, Diep BA, Otto M. Host defense and pathogenesis in Staphylococcus aureus infections. Infect Dis Clin North Am 2009;23:17-34.
25. DeLeo F, Chambers HF. Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. J Clin Invest 2009;119:2464-2474.
26. Foster TJ. Antibiotic resistance in Staphylococcus aureus. current status and future prospects. FEMS Microbiol Rev 2017;41:430-449.
27. Thai T, Salisbury BH, Zito PM (2021). Ciprofloxacin. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
28. Sharma PC, Jain A, Jain S, Pahwa R, Yar MS. Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspects. J Enzyme Inhib Med Chem 2010;25:577-589.
29. Ołdak A, Zielińska D, Rzepkowska A, Kołożyn-Krajewska D. Comparison of antibacterial activity of Lactobacillus plantarum strains isolated from two different kinds of regional cheeses from Poland: Oscypek and Korycinski cheese. Biomed Res Int 2017;2017:6820369.
30. Pankey GA, Sabath LD. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections. Clin Infec Dis 2004;38:864-870.
31. Ocampo PS, Lazar V, Papp B, Arnoldini M, Abel Zur Wiesch P, Busa-Fekete R, et al. Antagonism between bacteriostatic and bactericidal antibiotics is prevalent. Antimicrob Agents Chemother 2014;58:4573-4582.
32. Nemeth J, Oesch G, Kuster SP. Bacteriostatic versus bactericidal antibiotics for patients with serious bacterial infections: systematic review and meta-analysis. J Antimicrob Chemother 2015;70:382-395.
33. Soares GM, Figueiredo LC, Faveri M, Cortelli SC, Duarte PM, Feres M. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs. J Appl Oral Sci 2012;20:295-309.
34. Ramachandran R, Chalasani AG, Lal R, Roy U. A broad-spectrum antimicrobial activity of Bacillus subtilis RLID 12.1. ScientificWorldJournal 2014;2014:968487.
35. Breijyeh Z, Jubeh B, Karaman R. Resistance of gram-negative bacteria to current antibacterial agents and approaches to resolve it. Molecules 2020;25:1340.
36. Kırmusaoğlu S, Gareayaghi N, Kocazeybek BS (2019). Introductory chapter : the action mechanisms of antibiotics and antibiotic resistance. In: Antimicrobials, antibiotic resistance, antibiofilm strategies and activity methods. Intechopen, 1st ed. London, UK, pp.1-9.
37. Eyler RF, Shvets K. Clinical pharmacology of antibiotics. Clin J Am Soc Nephrol 2019;14:1080-1090.
38. El-Attar MAZ, Elbayaa RY, Shaaban OG, Habib NS, Abdel Wahab AE, Abdelwahab IA, et al. Design, synthesis, antibacterial evaluation and molecular docking studies of some new quinoxaline derivatives targeting dihyropteroate synthase enzyme. Bioorg Chem 2018;76:437-448.
39. Ferreira LG, Dos Santos RN, Oliva G, Andricopulo AD. Molecular docking and structure-based drug design strategies. Molecules 2015;20:13384-13421.
40. Masters PA, O’Bryan TA, Zurlo J, Miller DQ, Joshi N. Trimethoprim-sulfamethoxazole revisited. Arch Intern Med 2003;163:402-410.
41. Kordus SL, Baughn AD. Revitalizing antifolates through understanding mechanisms that govern susceptibility and resistance. Medchemcomm 2019;10:880-895.
42. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochemistry 2014;53:1565-1574.
43. Öztürk H, Ozkirimli E, Özgür A. Classification of beta-lactamases and penicillin binding proteins using ligand centric network models. PLoS One 2015;10(2):e0117874.
| Files | ||
| Issue | Vol 13 No 4 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v13i4.6981 | |
| Keywords | ||
| Antibiotics; Endosimbiotic bacteria; Endosymbiotic bacterial compound; Pheretima sp. | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Husain D, Wardhani R. Antibacterial activity of endosymbiotic bacterial compound from Pheretima sp. earthworms inhibit the growth of Salmonella Typhi and Staphylococcus aureus: in vitro and in silico approach. Iran J Microbiol. 2021;13(4):537-543.
