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Computational discovery of putative quorum sensing inhibitors against LasR and RhlR receptor proteins of Pseudomonas aeruginosa

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Abstract

Drugs have been discovered in the past mainly either by identification of active components from traditional remedies or by unpredicted discovery. A key motivation for the study of structure based virtual screening is the exploitation of such information to design targeted drugs. In this study, structure based virtual screening was used in search for putative quorum sensing inhibitors (QSI) of Pseudomonas aeruginosa. The virtual screening programme Glide version 5.5 was applied to screen 1,920 natural compounds/drugs against LasR and RhlR receptor proteins of P. aeruginosa. Based on the results of in silico docking analysis, five top ranking compounds namely rosmarinic acid, naringin, chlorogenic acid, morin and mangiferin were subjected to in vitro bioassays against laboratory strain PAO1 and two more antibiotic resistant clinical isolates, P. aeruginosa AS1 (GU447237) and P. aeruginosa AS2 (GU447238). Among the five compounds studied, except mangiferin other four compounds showed significant inhibition in the production of protease, elastase and hemolysin. Further, all the five compounds potentially inhibited the biofilm related behaviours. This interaction study provided promising ligands to inhibit the quorum sensing (QS) mediated virulence factors production in P. aeruginosa.

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Acknowledgments

We extend our sincere thanks to computational and bioinformatics facility provided by the Alagappa University Bioinformatics Infrastructure Facility (funded by the Department of Biotechnology, Government of India; Grant No. BT/BI/25/001/2006). We thank Schrodinger, LLC, New York, USA for providing free access of their bioinformatics tools. We also extend our sincere thanks to Dr. K. Syed Ibrahim, Research Associate, Department of Biotechnology, Mizoram University, Aizawl and Mr. C. Selvaraj, Research Scholar, Department of Bioinformatics, Alagappa University, Karaikudi for their assistance in the bioinformatics part of this manuscript. A. Annapoorani gratefully acknowledges the Council of Scientific and Industrial Research (CSIR), New Delhi for the financial assistance rendered [CSIR SRF No. 9/688 (0014)/2011].

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Authors and Affiliations

  1. Department of Biotechnology, Alagappa University, Karaikudi, 630 003, Tamil Nadu, India

    Angusamy Annapoorani, Venugopal Umamageswaran, Radhakrishnan Parameswari, Shunmugiah Karutha Pandian & Arumugam Veera Ravi

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  1. Angusamy Annapoorani
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  2. Venugopal Umamageswaran
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  3. Radhakrishnan Parameswari
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  4. Shunmugiah Karutha Pandian
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  5. Arumugam Veera Ravi
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Correspondence to Arumugam Veera Ravi.

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Annapoorani, A., Umamageswaran, V., Parameswari, R. et al. Computational discovery of putative quorum sensing inhibitors against LasR and RhlR receptor proteins of Pseudomonas aeruginosa . J Comput Aided Mol Des 26, 1067–1077 (2012). https://doi.org/10.1007/s10822-012-9599-1

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  • DOI: https://doi.org/10.1007/s10822-012-9599-1

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