ارزیابی بیوانفورماتیکی تأثیر ترکیبات گیاهی موجود در گیاهان دارویی Hyssopus officinalis L. ، Tragopogon graminifolius و Avicennia marina L. در مهار پروتئین‌های مؤثر در بروز مقاومت آنتی‌بیوتیکی در Acinetobacter baumannii

نوع مقاله : مقاله پژوهشی

نویسنده

مرکز آموزش عالی کشاورزی بردسیر - دانشگاه باهنر کرمان - کرمان

10.22103/jab.2021.17570.1315

چکیده

هدف: استینوباکتر بومانی باکتری مهمی در ایجاد عفونت­های بیمارستانی می­باشد که مقاومت چند دارویی دارد. چندین عامل در مقاوم شدن این باکتری­ها در برابر داروها نقش دارند که مهم­ترین آن­ها پروتئین­های OXA-24 beta-lactamase، OXA-23 beta-lactamase وOUTER MEMBRANE PROTEIN A (OMPA)  هستند. در همین راستا هدف از این مطالعه بررسی اثر مهارکنندگی ترکیبات گیاهی موجود در گیاهان دارویی شنگ، زوفا و مانگرو بر این پروتئین­های استینوباکتر در محیط in silico می­باشد.
مواد و روش‌ها: در این پژوهش نخست ساختار ترکیبات گیاهی  و پروتئین­های مورد بررسی به ترتیب از پایگاه­های  PubChem  و PDB دریافت و سپس خصوصیات فیزیکوشیمیایی ترکیبات گیاهی و همین­طور پتانسیل جهش­زایی آن­ها به ترتیب توسط سرور Swiss ADME  و نرم­افزار Toxtree-v2.6.13 پیش­بینی شدند. برای انجام داکینگ مولکولی و برهمکنش میان ترکیبات گیاهی و پروتئین­های مورد نظر از محیط­های ViewerLite، Chimera 1.14، Discovery Studio ، AutoDockTools-1.5.6  و AutoDock Vina استفاده شد. در نهایت، نتایج با استفاده از سه برنامه AutoDockTools ،Visualizer DS و Ligplot مورد آنالیز قرار گرفت.
نتایج: پتانسیل جهش­زایی و مهار سیتوکروم­ها نشان دادند ترکیبات مربوط به H. officinalis پتانسیل جهش­زایی و سمیت سلولی بالاتری نسبت به دو گیاه دیگر داشتند. علاوه بر این، نتایج نشان داد که ترکیبات گیاهی A. marina  جذب گوارشی بالاتری در مقایسه با سایر ترکیبات دارند. بررسی مقایسه­ای برهمکنش­ها نشان داد که ترکیبات گیاه H. officinalis و A. marina  برهمکنش­های قوی­تری را با پروتئین­های مورد بررسی انجام می­دهند. علاوه بر این مشخص شد قوی­ترین برهمکنش­های رخ داده بین ترکیبات گیاهی و پروتئین 1BXWمی­باشد. از طرف دیگر مشخص شد ترکیبات گیاه T. graminifolius برهمکنش­های ضعیف­تری را با پروتئین­های مورد ارزیابی ایجاد می­کنند.
نتیجه‌گیری: بر اساس نتایج به دست آمده از مطالعات داکینگ، در میان تمام ترکیبات مورد ارزیابی در هر سه پروتئین 1BXW، 3G4P و4K0X ، بهترین نتایج داکینگ مربوط به ترکیبات cis-pinocamphone و3,5-difluorophenyl ester 2,6-difluorobenzoic acid به ترتیب از گیاهان زوفا و مانگرو است. در حقیقت این ترکیبات با منفی­ترین سطح انرژی اتصال (به ترتیب  Kcal/mol9- و 8/8-) تمایل بیشتری برای اتصال به آمینواسیدهای کلیدی جایگاه فعال هر سه پروتئین مورد مطالعه دارد. بنابراین ترکیبات مذکور می­توانند به عنوان نامزدهای بسیار مناسبی برای بررسی آزمایشگاهی و in vivo فعالیت ضد A. baumannii محسوب شوند.

کلیدواژه‌ها


عنوان مقاله [English]

Bioinformatics evaluation of the compounds effect of medicinal plants Hyssopus officinalis L., Tragopogon graminifolius and Avicennia marina L. on the inhibition of effective proteins against antibiotic resistance in Acinetobacter baumannii

نویسنده [English]

  • Marzieh Etehadpour
Bradsir Agricultural Excellence Training Center - Shahid Bahonar University of kerman, - Kerman
چکیده [English]

Objective
Acinetobacter baumannii is an important bacterium in causing nosocomial infections that has multidrug resistance. Several factors are involved in the resistance of these bacteria to drugs, the most important of which are the proteins OXA-24 beta-lactamase, OXA-23 beta-lactamase and OUTER MEMBRANE PROTEIN A (OMPA). In this regard, the aim of this study was to investigate the inhibitory effect of plant compounds in Salsify, Hyssop and Mangrove on these Acinetobacterproteins in silico.
 
Materials and methods
In this study, first the structure of plant compounds and proteins were obtained from PubChem and PDB databases, respectively. Then the physicochemical properties and mutagenic potential of plant compounds were predicted by Swiss ADME server and Toxtree-v2.6.13 software, respectively. ViewerLite, Chimera 1.14, Discovery Studio, AutoDockTools-1.5.6 and AutoDock Vina environments were used for molecular docking and interaction between plant compounds and proteins. The results were analyzed using three programs including  AutoDockTools, Visualizer DS and Ligplot.
 
Results
According to mutagenicity potential and inhibition cytochromes results, compounds related to H. officinalis had higher mutagenic potential and cytotoxicity than the other two plants. In addition, the results showed that A. marina compounds have higher digestive absorption compared to other compounds. A comparative study of the interactions showed that the compounds of H. officinalis and A. marina have stronger interactions with the studied proteins. In addition, it was found that the strongest interactions occurred between plant compounds and 1BXW protein. On the other hand, T. graminifolius compounds were found to have weaker interactions with the evaluated proteins.
 
Conclusions
Based on docking results, among all compounds evaluated in all three proteins 1BXW, 3G4P and 4 K0X, the best docking results were related to cis-pinocamphone and 3,5-difluorophenyl ester 2,6-difluorobenzoic acid, respectively, from Hyssop and mangrove. In fact, these compounds with the most negative binding energy levels (-9 Kcal / mol and -8.8, respectively) have a greater tendency to bind to the key amino acids of the active site of all three proteins. Therefore, these compounds can be considered as important candidates for laboratory and in vivo testing of A. baumannii activity.

کلیدواژه‌ها [English]

  • Molecular docking
  • bioinformatics
  • Beta-lactamase
  • Medicinal plants
حسن شاهیان م، سعادت فر ا، معصومی ف (2019) بررسی خواص ضد میکروبی گیاه زوفا (Hyssopus officinalisis) علیه باکتری‌های بیماریزای مقاوم به انتی بیوتیک در فرم منفرد و بیوفیلم. زیست شناسی میکروارگانیسم ها 7، 91-101.
قاسمی م، حبیبی ر، صدیقی م و همکاران (2019) اثر ضد باکتریایی عصاره هیدروالکلی گیاه شنگ روی اسینتوباکتر بائومانی در شرایط آزمایشگاهی. بیماریهای عفونی و گرمسیری 22، 41-45.
محمودپور م، عسکری ا، یوسفی ف و همکاران (2019) بررسی اثرات ضد باکتریایی عصاره خام برگ گیاه حرا بر روی سویه‌های استاندارد و بالینی Acinetobacter baumannii  در شرایط In-vitro. طب جنوب 22، 150-159.
نجف پور نوایی م، میرزا م (2003) مقایسه ترکیبهای شیمیایی اسانس برگ گیاه زوفا (Hyssopus officinalis L.) در شرایط کشت و رویشگاه طبیعی. تحقیقات گیاهان دارویی و معطر ایران 18، 43-51.
 
References
Amir GZ, Azadbakht M, Keshavarzi F (2000) Echium amoenum stimulate of lymphocyte proliferation and inhibit of humoral antibody synthesis. Iran J Med Sci 25, 119-124.
Bandaranayake WM (2002) Bioactivities, bioactive compounds and chemical constituents of mangrove plants. Wetlands Ecol Manage 10, 421-452.
Bayram Y, Parlak M, Aypak C et al. (2013) Three-year review of bacteriological profile and antibiogram of burn wound isolates in Van, Turkey. Int J Med Sci 10, 19-22.
Blundell TL, Sibanda BL, Montalvão RW et al. (2006) Structural biology and bioinformatics in drug design: opportunities and challenges for target identification and lead discovery. Philosophical Transactions of the Royal Society B: Biol Sci 361, 413-423.
Chakraborty B, Nath A, Saikia H et al. (2014) Bactericidal activity of selected medicinal plants against multidrug resistant bacterial strains from clinical isolates. Asian Pac J Trop Med 7s1, S435-441.
Daina A, Michielin O, and Zoete V (2017) SwissADME: A Free Web Tool To Evaluate Pharmacokinetics, Drug-likeness and Medicinal Chemistry Friendliness of Small Molecules. Sci Rep 7, 1–13.
DeLano WL (2002) The PyMOL molecular graphics system. San Carlos, CA: DeLano Scientific LLC.
Farhoudi R (2013) Effect of drought stress on chemical constituents, photosynthesis and antioxidant properties of Rosmarinus officinalis essential oil. J Med Plant By-Product 2, 17-22.
Fathiazad F, Hamedeyazdan S (2011) A review on Hyssopus officinalis L.: Composition and biological activities. Afr J Pharm Pharmacol 5, 1959-1966.
Figueiredo AC, Barroso JG, Pedro LG et al. (2008) Factors affecting secondary metabolite production in plants: volatile components and essential oils. Flavour Fragrance J 23, 213-226.
Ghasemi M, Habibi R, Sedighi M et al. (2019) Antibacterial effect of Tragopogon graminifolius DC hydroalcoholic extracts on Acinetobacter baumannii (In vitro study). Iran J Infect Dis Trop Med 22,41-45.
Guedes IA, de Magalhães CS, Dardenne LE (2017) Receptor-Ligand Molecular Docking. Biophys Rev 6, 75-87.
Hanwell MD, Curtis DE, Lonie DC et al (2012) Avogadro: An Advanced Semantic Chemical Editor, Visualization, and Analysis Platform. J Cheminform 4, 1-17.
Hassanshahian M, Saadatfar A, Masoumi F (2019) Antimicrobial properties of Hyssopus officinalis extract against antibiotic resistant bacteria in planktonic and biofilm form. Biol J Microorganism 7, 91-101.
Heidari MR, Azad EM, Mehrabani M (2006) Evaluation of the analgesic effect of Echium amoenum Fisch & CA Mey. extract in mice: possible mechanism involved. J Ethnopharmacol 103, 345-349.
Jahani S, Saeidi S, Javadian F et al. (2016) Investigating the antibacterial effects of plant extracts on Pseudomonas aeruginosa and Escherichia coli. Int J Infect 3, 1-5.
Jeon JH, Lee JH, Lee JJ et al. (2015) Structural basis for carbapenem-hydrolyzing mechanisms of carbapenemases conferring antibiotic resistance. Int J Mol Sci 16, 9654-9692.
Karmostaji A, Najar Peerayeh S, Hatef Salmanian A (2013) Distribution of OXA-type class D β-lactamase genes among nosocomial multi drug resistant Acinetobacter baumannii isolated in Tehran hospitals. Jundishapur J Microbiol 6, 15-21.
Kreis W, Kaplan MH, Freeman J et al. (1990) Inhibition of HIV replication by Hyssop officinalis extracts. Antiviral Res 14, 323-337.
Laskowski RA, Swindells MB (2011) LigPlot+: multiple ligand–protein interaction diagrams for drug discovery. J Chem Inform Model 51, 2778-86.
Letessier M, Svoboda K, Walters D (2001) Antifungal activity of the essential oil of hyssop (Hyssopus officinalis). J Phytopathol 149, 673-678.
Lin M-F, Lan C-Y (2014) Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside. World Journal of Clinical Cases: WJCC 2, 787.
Mahmudpour M, Askari A, Yousefi F (2019) Antibacterial effect leaf extract of Avicennia marina on standard and clinical strains of Acinetobacter baumannii. Iran South Med J 22, 150-159. 
Marino M, Bersani C, Comi G (2001) Impedance measurements to study the antimicrobial activity of essential oils from Lamiaceae and Compositae. Int J Food Microbiol 67, 187-195.
Mashhady MA, Abkhoo J, Jahani S et al. (2016) Inhibitory effects of plant extracts on Pseudomonas aeruginosa biofilm formation. Int J Infect 3, 34-41.
Merkier AK, Centrón D (2006) blaOXA-51-type β-lactamase genes are ubiquitous and vary within a strain in Acinetobacter baumannii. Int J Antimicrob Agent 28, 110-113.
Mimica-Dukić N, Bugarin D, Grbović S et al. (2010) Essential oil of Myrtus communis L. as a potential antioxidant and antimutagenic agents. Molecule 15, 2759-2770.
Molecular Property Predictions Osiris Property Explorer, From: http://www.cheminformatics.ch/propertyExplorer/, Accessed 6 July 2013.
Morris GM, Huey R, Lindstrom W et al (2009) Autodock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 30, 2785–2791.
Najafpour Navaei M, Mirza M (2003) Comparative study on the essential oil composition of the leaves of Hyssopus officinalis L. in field and wild growing. Iran J Med Aromatic Plant Res 18, 43-51.
Nosrati M, Behbahani M (2016) In vitro and in silico evaluation of antibacterial effect of methanolic extracts of Prangos ferulacea on single and biofilm structure of Streptococcus mutans. SSU-J 23, 1049-1062.
Nosrati M, Shakeran Z, Shakeran Z (2018) Frangulosid as a novel hepatitis B virus DNA polymerase inhibitor: a virtual screening study. In silico Pharmacol 6, 1-9.
Özer H, Sökmen M, Güllüce M et al. (2006) In vitro antimicrobial and antioxidant activities of the essential oils and methanol extracts of Hyssopus officinalis L. ssp. angustifolius Ital J Food Sci 18, 90-99.
Peleg AY, Seifert H, Paterson DL (2008) Acinetobacter baumannii: emergence of a successful pathogen. Clinic Microbiol Rev 21, 538-582.
Pettersen EF, Goddard TD, Huang CC et al. (2004) UCSF Chimera–a visualization system for exploratory research and analysis. J Comput Chem 25, 1605–1612.
Pirbalouti AG, Malekpoor F, Salimi A et al. (2017) Effects of foliar of the application chitosan and reduced irrigation on essential oil yield, total phenol content and antioxidant activity of extracts from green and purple basil. Acta Sci Pol Hortorum Cultus 16, 177-186.
Poirel L, Mansour W, Bouallegue O et al. (2008) Carbapenem-resistant Acinetobacter baumannii isolates from Tunisia producing the OXA-58-like carbapenem-hydrolyzing oxacillinase OXA-97. Antimicrob Agent Chemotherapy 52, 1613-1617.
Poirel L, Marqué S, Héritier C et al. (2005) OXA-58, a novel class D β-lactamase involved in resistance to carbapenems in Acinetobacter baumannii. Antimicrob Agent Chemotherapy 49, 202-208.
Pradhan J, Sahoo S, Lalotra S et al. (2017) Positive impact of abiotic stress on medicinal and aromatic plants. Int J Plant Sci (Muzaffarnagar) 12, 309-313.
Ranjbar A, Khorami S, Safarabadi M et al. (2006) Antioxidant activity of Iranian Echium amoenum Fisch & CA Mey flower decoction in humans: a cross-sectional before/after clinical trial. Evidence-Based Complementary Alternative Med 3, 469-473.
Ravikumar S, Gnanadesigan M, Suganthi P et al. (2010) Antibacterial potential of chosen mangrove plants against isolated urinary tract infectious bacterial pathogens. Int J Med Med Sci 2, 94-99.
Saad S, Taher M, Susanti D et al. (2012) In vitro antimicrobial activity of mangrove plant Sonneratia alba. Asian Pacific J Trop Biomed 2, 427-429.
Saeidi S, Shiri Y, Bokaeian M et al. (2014) Antibacterial activity of essential oil of Sature jahortensis against multi-drug resistant bacteria. Int J Enteric Pathog 2, 1-4.
Said-Al Ahl HA, Abbas ZK, Sabra AS et al. (2015) Essential oil composition of Hyssopus officinalis L. cultivated in Egypt. Int J Plant Sci Ecol 1, 49-53.
Sato M, Tsuchiya H, Akagiri M et al. (1997) Growth inhibition of oral bacteria related to denture stomatitis by anti‐candidal chalcones. Aust Dental J 42, 343-346.
Savithramma N, Rao ML, Suhrulatha D (2011) Screening of medicinal plants for secondary metabolites. Middle-East J Sci Res 8, 579-584.
Savoia D (2012) Plant-derived antimicrobial compounds: alternatives to antibiotics. Future Bicrobiol 7, 979-990.
Smani Y, Fàbrega A, Roca I et al. (2014) Role of OmpA in the multidrug resistance phenotype of Acinetobacter baumannii. Antimicrob Agent Chemother 58, 1806-1808.
Smith CA, Antunes NT, Toth M et al. (2014) Crystal structure of carbapenemase OXA-58 from Acinetobacter baumannii. Antimicrob Agents Chemother 58, 2135-2143.
Spence RP, Towner KJ, Henwood CJ et al. (2002) Population structure and antibiotic resistance of Acinetobacter DNA group 2 and 13TU isolates from hospitals in the UK. J Med Microbiol 51, 1107-1112.
Srivastava A, Awasthi K, Kumar B et al. (2018) Pharmacognostic and pharmacological evaluation of Hyssopus officinalis L.(Lamiaceae) collected from Kashmir Himalayas, India. Pharmacognosy J 10, 1-9.
Talei GR, Meshkatalsadat MH, Mosavi SZ (2008) Antibacterial activity native medicinal plants extracts in Lorestan, Iran. J Gorgan Uni Med Sci 10, 31-35.
Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comp Chem 31, 455-461.
Turton JF, Woodford N, Glover J et al. (2006) Identification of Acinetobacter baumannii by detection of the blaOXA-51-like carbapenemase gene intrinsic to this species. J Clinic Microbiol 44, 2974-2976.
Vallejo MCG, Herraiz JG, Pérez-Alonso MJ et al. (1995) Volatile oil of Hyssopus officinalis L. from Spain. J Essential Oil Res 7, 567-568.
Weinstein RA (2001) Controlling antimicrobial resistance in hospitals: infection control and use of antibiotics. Emerging Infect Disease 7, 188.
Zawiślak G (2013) Morphological characters of Hyssopus officinalis L. and chemical composition of its essential oil. Modern Phytomorphol 4, 93-95.
Zidorn C, Ellmerer E, Sturm S et al. (2010) E and F from tragopogons and distribution of caffeic acids, lignans and tyrolobibenzyls in European taxa of the subtribe Scorzonerinae(Lactuceae, Asteraceae). Phytochem 63, 61-67.