Email this article 
Senyawa Alami Bawang Putih Tunggal sebagai Inhibitor LpxC Bakteri Pseudomonas aeruginosa melalui Virtual Screening
Abstract
Pseudomonas aeruginosa merupakan salah satu bakteri Gram negatif penyebab infeksi nosokomial yang memiliki resistensi tinggi terhadap berbagai antibiotik karena adanya lipid A, komponen LPS bersifat toksik pada inang. Sintesis lipid A dimulai dari Kdo2 -lipid A, difasilitasi oleh enzim LpxC. Enzim LpxC merupakan target pengembangan antibiotik karena adanya kofaktor Zn2+. Bawang putih tunggal merupakan herbal potensial pengganti antibiotik sintetis. Alliin, Allicin dan Ajoene yang terkandung dalam bawang putih tunggal memiliki aktivitas antibakteri. Penelitian ini bertujuan memprediksi potensi senyawa organosulfur bawang putih tunggal sebagai agen antibakteri melalui virtual screening menggunakan metode molecular docking. Metode yang dilakukan adalah memprediksi potensi senyawa organosulfur menggunakan web server PASS dan melakukan docking untuk mengetahui interaksi ligan-protein target. Hasil penelitian menunjukkan, senyawa organosulfur berpotensi sebagai antibakteri, antibiotik, dan immunomodulator. Aktivitas antibakteri terbaik ditunjukkan oleh senyawa Alliin dengan nilai afinitas pengikatan -5,2 kkal/mol. Semua senyawa organosulfur memiliki sisi aktif yang sama dengan kontrol (Ciprofloxacin dan Imipenem) pada enzim LpxC. Sisi aktif ditunjukkan dengan adanya residu asam amino (Ser295, Val182, dan Tyr 296) yang berikatan dengan ikatan hidrogen dan interaksi hidrofobik (Phe152, Phe181, Gly85, Phe176, Ala84, Val182, Ser180, Ile241, Leu86, Tyr296, Ser295 dan Met297) antara ligan-protein target.
Keywords
Full Text:
Download ArticleReferences
Amagase, H., Petesch, B.L., Matsuura, H., Kasuga, S. & Itakura, Y. 2001. Intake of Garlic and Its Bioactive Compounents. The Journal of Nutrition.
Amudha, M. & Rani, S. 2016. In Silico Molecular Docking Studies on the Phytoconstituents of Cadaba Fruticosa (L.) Druce for Its Fertility Activity. Asian J Pharm Clin Res, 9 (2): 48-50.
Atkovska, K., Samsonov, S.A., Paszkowski-Rogacz, M. & Pisabarro, M. T. 2014. Multipose Binding in Molecular Docking. Int. J. Mol. Sci., 15, 2622-2645. DOI: 10.3390/ijms15022622.
Davis, A.M. & Teague, S.J. 1999. Hydrogen Bonding, Hydrophobic Interaction, and Faiilure of the Rigid Receptor Hypothesis. Angew Chem Int Ed, 38, 736-749.
Doerrler, W. T. 2006. Lipid Trafficking to the Outer Membrane of Gram-negative Bacteria. Mol Microbiol, 60: 542–52.
Dusica, P.I., Vesna, D.N., Ljubisa, B.N., Mihajlo, Z.S. & Ljiljana, P.S. 2010. Thermal Degradation, Antioxidant and Antimicrobial Activity of the Synthesized Allicin and Allicin Incorporated in Gel. 2010. Hem. Ind, 64(2), 85-91. DOI: 10.2298/HEMIND091111003l.
Elokely, K.M. & Doerksen, R.J. 2013. Docking Challenge: Protein Sampling and Molecular Docking Performance. J. Chem. Inf. Model, 53, 1934-1945.
Feng, Y., Zhu, X. & Wang, Q. 2012. Allicin Enhances Host Pro-Inflammatory Imune Respoonses and Protects Against Acute Murine Malaria Infection. Malaria Journal. DOI: 100.1186/1475-2875-11-268.
Horan, T. C., Andrus, M. & Dudeck, M. A. 2008. CDC/NHSN Surveillance Definition of Health Care-Associated Infection and Criteria for Specific Types of Infection in the Acute Care Setting. Am J Infect Control, 36 (5): 309-332.
Ichsan, B. Z. 2009. Efek Antibakteri Ekstrak Bawang Putih (Allium sativum) Terhadap Pertumbuhan Streptococcus mutans Secara in vitro. Skripsi tidak diterbitkan. Surakarta: Fakultas Kedokteran Universitas Sebelas Maret.
Jakobsen, T.H., Gennip, M., Phipps, R.k., Shanmugham, S., Christensen, L.D., Alhede, M., Skindersoe, M.E., Rasmussen, T.B., Friedrich, K., Uthe, F., Jensen, P.O., Moser, C., Nielsen, K.F., Eberi, L., Larsen, T.O., Tanner, D., Hoiby, N., Bjarnsholt, T. & Givskov, M. 2012. Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Gene Controlled by Quorum Sensing. Antimicrobal Agents and Chemotherapy, 56(5), 2314-2325. DOI: 10.1128/AAC05919-11.
Inweregbu, K., Dave, J. & Pittard, A. 2005. Nosocomial Infection. Continuing Education in Anaesthesia, Critical Care & Pain, 5 (1): 14-17.
Lagunin, A., Stepanchikova, A., Filimonov, D. & Poroikov, V. 2000. PASS: Prediction of Activity Spectra for Biologically Active Substances. Bioinformatics Applications Note, 16(8), 747-748.
Lestari, S. R. & Rifa’i, M. 2017. Daily Administration of Single Garlic Oil Extract in Mice as Sub-Chronic Toxicity Assesment. The 5th International Conference on Biological Sciences.
Madigan, M. T., Martinko, J. M., Stahl, D. A. & Clark, D. P. 2011. Brock: Biology of Microorganisms. Thirteenth Edition. US of America: Pearson.
Meng, X.Y., Zhang, H.X., Mezei, M. & Cui, M. 2011. Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery. Curr. Comput. Aided Drug Des, 7, 146-157.
Micek, S. T., Lloyd, A. E., Ritchie, D. J., Reichley, R. M., Fraser, V. J. & Kollef, M. H. 2005. Pseudomonas aeruginosa Bloodstream Infection: Importance of Appropriate Initial Antimicrobial Treatment. Antimicrobial Agents and Chemotherapy, 49 (4): 1306-1311.
Moehario, L. H., Hartono, T. S., Wardoyo, E. H. & Tjoa, E. 2012. Trend of Antibiotiks Susceptibility of Multidrugs Resistance Pseudomonas aeruginosa in Jakarta and Surrounding Areas From 2004 to 2010. African Journal of Microbiology Research, 6 (9): 2222-2229.
Ozer, B., Akkurt, C. O., Duran, N., Onlen, Y., Savas, L. & Turhanoglu, S. 2011. Evaluation of Nosocomial Infections and Risk Factors in Critically Ill Patients. Med Sci Monit, 17 (3): 17-22.
Parasuraman, S. 2011. Prediction of Activity Spectra for Substance. Journal of Pharmacology and Pharmacotherapeutics, 2(1), 52-53. DOI: 10.4103/0976-500X.77119.
Patil, R., Das, S., Stanley, A., Yadav, L., Sudhakar, A. & Varma, A.K. 2010. Optimized Hydrophobic Interactions and Hydrogen Bonding at the Target-Ligand Interface Leads the Pathways of Drug-Designing. Plos One, 5(8), 1-10. DOI: 10.1371/journal.pone.0012029.
Phalamthodi, S.M., Gaikwad, V.J., Ghasghase, N.V. & Patil, S.S. 2011. Antibacterial Targets in Pseusomonas aeruginosa. International Journal of Pharmaceutical Application, 2(3), 159-164. ISSN 0976-2639.
Qian, S., Waldron, L., Choudhary, N., Klevit, R.E., Chazin, W.J. & Patterson, C. 2009. Engineering a Ubiquitin Ligase Reveals Conformational Flexibility Required for Ubiquitin Transfer. The Journal of Biological Chemistry, 284(39), 26797-26802. DOI: 10.1074/jbcM109.032334.
Quintero-Fabian, S., Ortuno-Sahagun, D., Vazquez-Carrera, M. & Lopes-Roa, R.I. 2013. Allicin, a Garlic (Allium sativum) Compound, Prevents LPS-induced Inflammation in 3T3-L1 Adpose. Mediator of Inflamamation. DOI: 100.1155/2013/381815.381815.
Raetz, C. R. H. & Whitfield, C. 2002. Lipopolysaccharide endotoxins. Annu Rev Biochem, 71: 635–700.
Rehman, F. & Mairaj, S. 2013. Antimicrobial Studies of Allicin and Ajoene. Int J Pharm Bio Sci, 4(2), 1095-1105. ISSN 0975-6299.
Sahoo, M., Jena, L., Daf, S. & Kumar, S. 2016. Virtual Screening for Potential Inhibitors of NS3 Protein of Zika Virus. Genomics Inform, 14(3), 104-111. DOI: 10.5808/Gl.2016.14.3.104.
Sehgal, S.A., Khattak, N.A. & Mir, A. 2013. Structural, Phylogenetic and Docking Studies of D-amino Acid Oxidase Activator (DAOA), a Candidate Schizophrenia Gene. Theoretical Biology and Medical Modelling, 10(3), 1-13.
Tamber, S., Maier, E., Benz, R. & Hancock, R. E. W. 2007. Characterization of OpdH, a Pseudomonas aeruginosa Porin Involved in the Uptake of Tricarboxylates. Journal of Bacteriology, 189 (3): 929-939.
Wang, X. & Quinn, P. J. 2010. Lipopolysaccharide: Biosynthetic Pathway and Structure Modification. Progress in Lipid Research, 49: 97–107.
Washiya, Y., Nishikiwa, T. & Fujino, T. 2013. Enhancement of Intestinal IgA Production by Ajoene in Mice. Bioscience, Biotechnology and Biochemistry, 77(11), 2298-2301. DOI: 10.1271/bbb.130408.
Yoo, M., Lee, S., Lee, S., Seog, H. Shin, D. 2010. Validation of High Performance Liquid Chromatography Methods for Determination of Bioactive Sulfur Compound in Garlic Bulbs. Food Sci. Biotechnol, 19(6), 1619-1626. DOI: 10.1007/s10068-010-0229-1.
Zulkarnain, I. 2006. Buku Ajar Ilmu Penyakit Dalam: Infeksi Nosokomial. Edisi 4. Jakarta: Pusat Penerbitan Departemen Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Indonesia.
DOI: https://doi.org/10.18196/mm.180111
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Editorial Office:
Journal Room, G1 (Biomedic) Building, Ground Floor, Faculty of Medicine and Health Science Universitas Muhammadiyah Yogyakarta,
Jalan Lingkar Selatan (Brawijaya), Tamantirto, Kasihan, Bantul, Daerah Istimewa Yogyakarta, Indonesia
Phone: +62 274 387 656 (ext: 231)
WA : +62 811-2650-303
Website: http://journal.umy.ac.id/index.php/mm
E-mail: mmjkk@umy.university
Mutiara Medika: Jurnal Kedokteran dan Kesehatan is licensed under a Creative Commons Attribution 4.0 International License. View My Stats