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In Silico Pharmacology

, 5:12 | Cite as

Antiquorum sensing activity of silver nanoparticles in P. aeruginosa: an in silico study

  • Syed Ghazanfar Ali
  • Mohammad Azam Ansari
  • Qazi Mohd. Sajid Jamal
  • Haris M. Khan
  • Mohammad Jalal
  • Hilal Ahmad
  • Abbas Ali Mahdi
Original Research

Abstract

Pseudomonas aeruginosa an opportunistic pathogen regulates its virulence through Quorum sensing (QS) mechanism comprising of Las and Rhl system. Targeting of QS mechanism could be an ideal strategy to combat infection caused by P. aeruginosa. Silver nanoparticles (AgNPs) have been broadly applied as antimicrobial agents against a number of pathogenic bacterial and fungal strains, but have not been reported as an anti-QS agent. Therefore, the aim of present work was to show the computational analysis for the interaction of AgNPs with the QS system using an In silico approach. In silico studies showed that AgNPs got ‘locked’ deeply into the active site of respective proteins with their surrounding residues. The molecular docking analysis clearly demonstrated that AgNPs got bound to the catalytic cleft of LasI synthase (Asp73-Ag = 3.1 Å), RhlI synthase (His52-Ag = 2.8 Å), transcriptional receptor protein LasR (Leu159-Ag = 2.3 Å) and RhlR (Trp10-Ag = 3.1 Å and Glu34-Ag = 3.2 Å). The inhibition of LasI/RhlI synthase by AgNPs blocked the biosynthesis of AHLs, thus no AHL produced, no QS occurred. Further, interference with transcriptional regulatory proteins led to the inactivation of LasR/RhlR system that finally blocked the expression of QS-controlled virulence genes. Our findings clearly demonstrate the anti-QS property of AgNPs in P. aeruginosa which could be an alternative approach to the use of traditional antibiotics for the treatment of P. aeruginosa infection.

Keywords

In silico Molecular docking Quorum sensing Pseudomonas aeruginosa Virulence Silver nanoparticles 

Notes

Acknowledgments

Mr. Syed Ghazanfar Ali is grateful to UGC, New Delhi, India for research assistance. Authors thank to Aligarh Muslim University, Aligarh, India and IRMC, University of Dammam, Saudi Arabia for providing instruments facilities and other items used in this study.

Compliance with ethical standards

Funding

None.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human or animals performed by any of the authors.

References

  1. Ali SG, Ansari MA, Khan HM, Jalal M, Mahdi AA, Cameotra SS (2017) Crataeva nurvala nanoparticles inhibit virulence factors and biofilm formation in clinical isolates of Pseudomonas aeruginosa. J Basic Microbiology 57:193–203CrossRefGoogle Scholar
  2. Alvarez MV, Moreira MR, Ponce A (2012) Antiquorum sensing and antimicrobial activity of natural agents with potential use in food. J Food Saf 32:379–387CrossRefGoogle Scholar
  3. Banik SK, Fenley AT, Kulkarni RV (2009) A model for signal transduction during quorum sensing in Vibrio harveyi. Phys Biol 6:046008CrossRefPubMedGoogle Scholar
  4. Benkert P, Biasini M, Schwede T (2011) Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27:343–350CrossRefPubMedGoogle Scholar
  5. Davies D (2003) Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov 2:114–122CrossRefPubMedGoogle Scholar
  6. Delden CV, Iglewski BH (1998) Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerg Infect Dis 4:551–560CrossRefPubMedPubMedCentralGoogle Scholar
  7. Gnanendra TS, Geethu G, Arjunan S, Sharmila B, Hussain MIZ, Moorthy K, Jeyakumar N (2010) Theoretical models of quorum sensing dependent regulation of transcriptional activators of Pseudomonas aeruginosa. Inter J Biol Technol 1:43–49Google Scholar
  8. Guex N, Peitsch MC, Schwede T (2009) Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: a historical perspective. Electrophoresis 30:S162–S173CrossRefPubMedGoogle Scholar
  9. Hodgkinson JT, Galloway WRJD, Wright M, Mati IK, Nicholson RL, Welch M, Spring DR (2012) Design, synthesis and biological evaluation of non-natural modulators of quorum sensing in Pseudomonas aeruginosa. Org Biomol Chem 10:6032–6044CrossRefPubMedGoogle Scholar
  10. Hollingsworth SA, Karplus PA (2010) A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins. Biomol Concepts 1:271–283CrossRefPubMedPubMedCentralGoogle Scholar
  11. Juan C, Zamorano L, Perez JL, Ge Y, Oliver A (2010) Activity of a new antipseudomonal cephalosporin, CXA-101 (FR264205), against carbapenem resistant and multidrugresistant Pseudomonas aeruginosa clinical strains. Antimicrob Agents Chemother 54:846–851CrossRefPubMedGoogle Scholar
  12. Longo F, Rampioni G, Bondì R, Imperi F, Fimia GM, Visca P, Zennaro E, Leoni L (2013) A new transcriptional repressor of the Pseudomonas aeruginosa quorum sensing receptor gene lasR. PLoS ONE 8:e69554CrossRefPubMedPubMedCentralGoogle Scholar
  13. Lovell SC, Davis IW, Arendall WB III, de Bakker PIW, Word JM, Prisant MG, Richardson JS, Richard DC (2002) Structure validation by Calpha geometry: phi, psi and Cbeta deviation. Proteins Struct Funct Genet 50:437–450CrossRefGoogle Scholar
  14. Mühling M, Bradford A, Readman JW, Somerfield PJ, Handy RD (2009) An investigation into the effects of silver nanoparticles on antibiotic resistance of naturally occurring bacteria in an estuarine sediment. Mar Environ 68:278–283CrossRefGoogle Scholar
  15. Pal S, Tak YK, Song JM (2007) Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the gram-negative bacterium Escherichia coli. Appl Environ Microbiol 73:1712–1720CrossRefPubMedPubMedCentralGoogle Scholar
  16. Palmer KL, Mashburn LM, Singh PK, Whiteley M (2005) Cystic fibrosis sputum supports growth and cues key aspects of Pseudomonas aeruginosa physiology. J Bacteriol 187:5267–5277CrossRefPubMedPubMedCentralGoogle Scholar
  17. Passador L, Cook JM, Gambello MJ, Rust L, Iglewski BH (1993) Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication. Science 260:1127–1130CrossRefPubMedGoogle Scholar
  18. Pearson JP, Pesci EC, Iglewski BH (1997) Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of elastase and rhamnolipid biosynthesis genes. J Bacteriol 179:5756–5767CrossRefPubMedPubMedCentralGoogle Scholar
  19. Pesci EC, Milbank JB, Pearson JP, McKnight S, Kende AS, Greenberg EP, Iglewski BH (1999) Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa. Proc Natl Acad Sci 96:11229–11234CrossRefPubMedPubMedCentralGoogle Scholar
  20. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2011) UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612CrossRefGoogle Scholar
  21. Reading NC, Sperandio V (2006) Quorum sensing: the many languages of bacteria. FEMS Microbiol Lett 254:1–11CrossRefPubMedGoogle Scholar
  22. Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234:779–815CrossRefPubMedGoogle Scholar
  23. Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ (2005) PatchDock and SymmDock: servers for rigid and symmetric docking. Nucl Acids Res 33:W363–W367CrossRefPubMedPubMedCentralGoogle Scholar
  24. Singh BR, Singh BN, Singh A, Khan W, Naqvi AH, Singh HB (2015) Mycofabricated biosilver nanoparticles interrupt Pseudomonas aeruginosa quorum sensing systems. Sci Rep 5:13719CrossRefPubMedPubMedCentralGoogle Scholar
  25. Su HC, Ramkissoon K, Doolittle J, Clark M, Khatun J, Secrest A, Wolfgang MC, Giddings MC (2010) The development of ciprofloxacin resistance in Pseudomonas aeruginosa involves multiple response stages and multiple proteins. Antimicrob Agents Chemother 54:4626–4635CrossRefPubMedPubMedCentralGoogle Scholar
  26. Vyshnava SS, Kanderi DK, Panjala SP, Pandian K, Bontha RR, Goukanapalle PKR, Banaganapalli B (2016) Effect of silver nanoparticles against the formation of biofilm by Pseudomonas aeruginosa an in silico approach. Appl Biochem Biotechnol 180(3):426–437CrossRefPubMedGoogle Scholar
  27. Wagner VE, Filiatrault MJ, Picardo KF, Iglewski BH (2008) Pseudomonas aeruginosa virulence and pathogenesis issues. In: Cornelis P (ed) Pseudomonas genomics and molecular biology, 1st edn. Caister Academic Press, Norfolk, pp 129–158Google Scholar
  28. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of general amber force field. J Comput Chem 25:1157–1174CrossRefPubMedGoogle Scholar
  29. Wang J, Wang W, Kollman PA, Case DA (2006) Automatic atom type and bond type perception in molecular mechanical calculations. J Mol Graph Model 25:247–260CrossRefPubMedGoogle Scholar
  30. Wass MN, Kelley LA, Sternberg MJ (2010) 3DLigandSite: predicting ligand-binding sites using similar structures. Nucl Acids Res 38:469–473CrossRefGoogle Scholar
  31. Weir E, Lawlor A, Whelan A, Regan F (2008) The use of nanoparticles in antimicrobial materials and their characterization. Analyst 133:835–845CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Syed Ghazanfar Ali
    • 1
  • Mohammad Azam Ansari
    • 2
  • Qazi Mohd. Sajid Jamal
    • 3
  • Haris M. Khan
    • 1
  • Mohammad Jalal
    • 1
  • Hilal Ahmad
    • 4
  • Abbas Ali Mahdi
    • 5
  1. 1.Department of Microbiology, Nanotechnology and Antimicrobial Drug Resistance Research Laboratory, Jawaharlal Nehru Medical College and HospitalAligarh Muslim UniversityAligarhIndia
  2. 2.Department of Microbiology, Institute of Research and Medical Consultations (IRMC)University of DammamDammamSaudi Arabia
  3. 3.Department of Health Information Management, College of Applied Medical SciencesBuraydah CollegesBuraydahSaudi Arabia
  4. 4.Centre for Nanoscience and NanotechnologyJamia Millia IslamiaNew DelhiIndia
  5. 5.Departments of BiochemistryKing George Medical UniversityLucknowIndia

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