Advertisement

Molecular Modeling and Drug Design: A Contemporary Analysis in Vibrio cholerae

  • Mobashar Hussain Urf Turabe Fazil
  • K. Konda Reddy
  • Haushila Prasad Pandey
  • Sunil Kumar
Chapter

Abstract

Vibrio cholerae causes the diarrheal disease cholera. This microbe inhabits well in human host and aquatic environments. Excessive use of antibiotics has contributed to the emergence of antibiotic resistance in V. cholerae. Quorum sensing is one of the lucrative targets presently pursued for drug design in bacteria to encounter virulence. LuxO, a response regulator, is an important part of quorum-sensing machinery in V. cholerae contributing in biofilms and virulence machinery. In this chapter, we will concisely discuss the disease, its clinical display, and distinctive methodologies to find drug targets. As a treatise on the method of drug design in V. cholerae, we used our in silico model of LuxO in this chapter, to predict probable sites of interference, and then used these sites for in silico drug design.

Keywords

Vibrio cholerae Drug design Novel drug targets Quorum sensing 

References

  1. Albert MJ et al (1996) Phage specific for Vibrio cholerae O139 Bengal. J Clin Microbiol 34:1843–1845PubMedPubMedCentralGoogle Scholar
  2. Basu A et al (2000) Vibrio cholerae O139 in Calcutta, 1992–1998: incidence, antibiograms, and genotypes. Emerg Infect Dis 6:139–147CrossRefPubMedPubMedCentralGoogle Scholar
  3. Campos J et al (2003) VGJΦ, a novel filamentous phage of Vibrio cholerae, integrates into the same chromosomal site as CTXΦ. J Bacteriol 185:5685–5696CrossRefPubMedPubMedCentralGoogle Scholar
  4. Cassel D, Selinger Z (1977) Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. Proc Natl Acad Sci U S A 74:3307–3311CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chance MR et al (2002) Structural genomics: a pipeline for providing structures for the biologist. Protein Sci 11:723–738CrossRefPubMedPubMedCentralGoogle Scholar
  6. Chang B et al (1998) Filamentous bacteriophages of Vibrio parahaemolyticus as a possible clue to genetic transmission. J Bacteriol 180:5094–5101PubMedPubMedCentralGoogle Scholar
  7. Chen X et al (2002) Structural identification of a bacterial quorum-sensing signal containing boron. Nature 415:545–549CrossRefGoogle Scholar
  8. Ehara M et al (1997) Characterization of filamentous phages of Vibrio cholerae O139 and O1. FEMS Microbiol Lett 154:293–301CrossRefPubMedGoogle Scholar
  9. Faruque SM et al (2003) CTXphi-independent production of the RS1 satellite phage by Vibrio cholerae. Proc Natl Acad Sci U S A 100:1280–1285CrossRefPubMedPubMedCentralGoogle Scholar
  10. Fazil MHUT, Kumar S, Farmer R, Pandey HP, Singh DV (2012a) Binding efficiencies of carbohydrate ligands with different genotypes of cholera toxin B: molecular modeling, dynamics and docking simulation studies. J Mol Model 18(1):1–10CrossRefPubMedGoogle Scholar
  11. Fazil MH et al (2012b) Comparative structural analysis of two proteins belonging to quorum sensing system in Vibrio cholerae. J Biomol Struct Dyn 30(5):574–584CrossRefPubMedGoogle Scholar
  12. Gill DM, Rappaport RS (1979) Origin of the enzymatically active A1 fragment of cholera toxin. J Infect Dis 139:674–680CrossRefPubMedGoogle Scholar
  13. Grover PA, Kuntal H, Sharma V (2010) In silico prediction of drug targets in Vibrio cholerae. Protoplasma 248(4):799–804PubMedGoogle Scholar
  14. Hammer BK, Bassler BL (2003) Quorum sensing controls biofilm formation in Vibrio cholerae. Mol Microbiol 50:101–104CrossRefPubMedGoogle Scholar
  15. Hammer BK, Bassler BL (2009) Distinct sensory pathways in Vibrio cholerae El Tor and classical biotypes modulate cyclic dimeric GMP levels to control biofilm formation. J Bacteriol 191:169–177CrossRefPubMedGoogle Scholar
  16. Holmgren J et al (1989) New cholera vaccines. Vaccine 7:94–96CrossRefPubMedGoogle Scholar
  17. Howard Jones N (1979) Cholera nomenclature and nosology; a historical note. Bull WHO 51:317–324Google Scholar
  18. Huq A et al (1984a) Influence of water temperature, salinity, and pH on survival and growth of toxigenic Vibrio cholerae serovar 01 associated with live copepods in laboratory microcosms. Appl Environ Microbiol 48:420–424PubMedPubMedCentralGoogle Scholar
  19. Huq A et al (1984b) The role of planktonic copepods in the survival and multiplication of Vibrio cholerae in the aquatic environment. In: Colwell RR (ed) Vibrios in the environment. Wiley, New York, pp 521–534Google Scholar
  20. Ikema M, Honma Y (1998) A novel filamentous phage, fs-2, of Vibrio cholerae O139. Microbiology 144:1901–1906CrossRefPubMedGoogle Scholar
  21. Jobling MG, Holmes RK (1997) Characterization of hapR a positive regulator of the Vibrio cholerae HA/protease gene hap and its identification as a functional homologue of the Vibrio harveyi luxR gene. Mol Microbiol 26:1023–1034CrossRefPubMedGoogle Scholar
  22. Jouravleva EA et al (1998) Characterization and possible functions of a new filamentous bacteriophage from Vibrio cholerae O139. Microbiology 144:315–324CrossRefPubMedGoogle Scholar
  23. Kahn RA, Gilman AG (1984) ADP-ribosylation of Gs promotes the dissociation of its alpha and beta subunits. J Biol Chem 259:6235–6240PubMedGoogle Scholar
  24. King CA, Van Heyningen WE (1973) Deactivation of cholera toxin by a sialidase-resistant monosialosylganglioside. J Infect Dis 127:639–647CrossRefPubMedGoogle Scholar
  25. Lenz DH et al (2004) The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118:69–82CrossRefPubMedGoogle Scholar
  26. Levine MM, Tacket CO (1994) Recombinant live cholera vaccines. In: Wachsmuth IK, Blake PA, Olsvik O (eds) Vibrio cholerae and cholera: molecular to global perspectives. American Society for Microbiology, Washington, DC, pp 39–415Google Scholar
  27. Levine MM et al (1981) Duration of infection-derived immunity to cholera. J Infect Dis 143:818–820CrossRefPubMedGoogle Scholar
  28. Lionta E et al (2014) Structure-based virtual screening for drug discovery: principles, applications and recent advances. Curr Top Med Chem 14(16):1923–1938CrossRefPubMedPubMedCentralGoogle Scholar
  29. Miller MB et al (2002) Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. Cell 110:303–314CrossRefPubMedGoogle Scholar
  30. Moss J et al (1980) Activation of choleragen by thiol: protein disulfide oxidoreductase. J Biol Chem 255:11085–11087PubMedGoogle Scholar
  31. Nwaka S, Hudson A (2006) Innovative lead discovery strategies for tropical diseases. Nat Rev Drug Discov 5:941–955CrossRefPubMedGoogle Scholar
  32. Pierce NF (1973) Differential inhibitory effects of cholera toxoids and ganglioside on the enterotoxins of Vibrio cholerae and Escherichia coli. J Exp Med 137:1009–1023CrossRefPubMedPubMedCentralGoogle Scholar
  33. Ramamurthy T (2008) Antibiotic resistance in Vibrio cholera. In: Faruque SM, Nair GB (eds) Vibrio cholerae: genomics and molecular biology. Caister Academic Press, London, pp 191–207Google Scholar
  34. Sanchez, Holmgren J (2008) Cholera toxin structure, gene regulation and pathophysiological and immunological aspects. Cell Mol Life Sci 65:1347–1136CrossRefPubMedGoogle Scholar
  35. Singh DV et al (2001) Molecular analysis of Vibrio cholerae O1, O139, non-O1 and non-O139 strains: clonal relationships between clinical and environmental isolates. Appl Environ Microbiol 67:910–921CrossRefPubMedPubMedCentralGoogle Scholar
  36. Spangler BD (1992) Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiol Rev 56:622–647PubMedPubMedCentralGoogle Scholar
  37. Spyrakis F, Cavasotto CN (2015) Open challenges in structure-based virtual screening: receptor modeling, target flexibility consideration and active site water molecules description. Arch Biochem Biophys 583:105–119CrossRefPubMedGoogle Scholar
  38. Stokes HW, Hall RM (1989) A novel family of potentially mobile DNA elements encoding site-specific gene-integration functions: integrons. Mol Microbiol 3:1669–1683CrossRefPubMedGoogle Scholar
  39. Tacket CO et al (1999) Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor Inaba three months after vaccination. Infect Immun 67:6341–6345PubMedPubMedCentralGoogle Scholar
  40. Van Dellen KL, Watnick PI (2006) The Vibrio cholerae biofilm: a target for novel therapies to prevent and treat cholera. Drug Discov Today Dis Mech 3:261–266CrossRefGoogle Scholar
  41. Van Heyningen WE et al (1971) Deactivation of cholera toxin by ganglioside. J Infect Dis 124:415–418CrossRefPubMedGoogle Scholar
  42. Vance RE, Zhu J, Mekalanos JJ (2003) A constitutively active variant of the Quorum-Sensing regulator LuxO affects protease production and biofilm formation in Vibrio cholerae. Infect Immun 71(5):2571–2576CrossRefPubMedPubMedCentralGoogle Scholar
  43. Vitkup D et al (2000) Solvent mobility and the protein ‘Glass’ transition. Nat Struct Biol 7:34–38CrossRefPubMedGoogle Scholar
  44. Waldor MK, Mekalanos JJ (1996) Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272:1910–1914CrossRefPubMedGoogle Scholar
  45. Waldor MK, Tschape H, Mekalanos JJ (1996) A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139. J Bacteriol 178:4157–4165CrossRefPubMedPubMedCentralGoogle Scholar
  46. Zhu J et al (2002) Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci U S A 99:3129–3134CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Mobashar Hussain Urf Turabe Fazil
    • 1
  • K. Konda Reddy
    • 2
  • Haushila Prasad Pandey
    • 3
  • Sunil Kumar
    • 4
    • 5
  1. 1.Lee Kong Chian School of MedicineNanyang Technological UniversitySingaporeSingapore
  2. 2.Department of PharmacyNational University of SingaporeSingaporeSingapore
  3. 3.Department of BiochemistryNepalgunj Medical College, Chisapani Campus, Kathmandu UniversityNepalgunjNepal
  4. 4.Bioinformatics CentreInstitute of Life SciencesBhubaneswarIndia
  5. 5.ICAR-NBAIMMauIndia

Personalised recommendations