Advertisement

Combating Staphylococcal Infections Through Quorum Sensing Inhibitors

  • Nishant Kumar
  • Hansita Gupta
  • Neha Dhasmana
  • Yogendra Singh
Chapter

Abstract

Staphylococcus aureus is a clinically important pathogen mainly causing hospital borne infections. These bacterial infections range from mild skin infections to serious health threats like endocarditis, osteomyelitis, and pneumonia. Few strains have developed resistance against antibiotics used to treat S. aureus infections and are termed as Methicillin Resistant S. aureus strains. The pathogen releases Auto Inducing Peptides to establish cell density dependent inter-cell communication, also known as quorum sensing (QS). QS results in the expression of accessory gene regulator system. It causes successful biofilm formation and enhanced expression of toxins. QS mediated biofilm formation provides an additional resistance against the antibiotics used. An innovative therapeutic approach has been studied vastly in last decade to deal with severe infections using specific QS inhibitors (QSIs). This chapter comprehensively describes the QSIs studied to control the infections caused by S. aureus strains.

Keywords

Agr system Staphylococcus aureus Biofilm Inhibitors Quorum sensing RAP/TRAP 

Notes

Acknowledgements

This work is supported by J C Bose Fellowship (SERB) to YS and Research Grant by University of Delhi. NK is UGC-SRF. HG is Masters of Science in Zoology from University of Delhi. ND is Shyama Prasad Mukherjee Fellow (CSIR-SRF) and Fulbright-Nehru Doctoral Fellow (2015–16) at NIAID NIH.

Author Information

The authors declare no competing financial interests. Correspondence and requests for materials should be addressed to YS (ysinghdu@gmail.com).

References

  1. Agarwala M, Choudhury B, Yadav RN (2014) Comparative study of antibiofilm activity of copper oxide and iron oxide nanoparticles against multidrug resistant biofilm forming uropathogens. Indian J Microbiol 54:365–368.  https://doi.org/10.1007/s12088-014-0462-z CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ahiwale SS, Bankar AV, Tagunde S, Kapadnis BP (2017) A bacteriophage mediated gold nanoparticle synthesis and their anti-biofilm activity. Indian J Microbiol 57:188–194.  https://doi.org/10.1007/s12088-017-0640-x CrossRefPubMedPubMedCentralGoogle Scholar
  3. Balaban N, Goldkorn T, Nhan RT, Dang LB, Scott S, Ridgley RM, Rasooly A, Wright SC, Larrick JW, Rasooly R, Carlson JR (1998) Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus. Science 280:438–440.  https://doi.org/10.1126/science.280.5362.438 CrossRefPubMedGoogle Scholar
  4. Balaban N, Goldkorn T, Gov Y, Hirshberg M, Koyfman N, Matthews HR, Nhan RT, Singh B, Uziel O (2001) Regulation of Staphylococcus aureus pathogenesis via target of RNAIII-activating protein (TRAP). J Biol Chem 276:2658–2667.  https://doi.org/10.1074/jbc.M005446200 CrossRefPubMedGoogle Scholar
  5. Baldry M, Kitir B, Frøkiær H, Christensen SB, Taverne N, Meijerink M, Franzyk H, Olsen CA, Wells JM, Ingmer H (2016) The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions. PLoS One 11:e0145618.  https://doi.org/10.1371/journal.pone.0145618 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Boisset S, Geissmann T, Huntzinger E, Fechter P, Bendridi N, Possedko M, Chevalier C, Helfer AC, Benito Y, Jacquier A, Gaspin C, Vandenesch F, Romby P (2007) Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism. Genes Dev 21:1353–1366.  https://doi.org/10.1101/gad.423507 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Brackman G, Cos P, Maes L, Nelis HJ, Coenye T (2011) Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrob Agents Chemother 55:2655–2661.  https://doi.org/10.1128/aac.00045-11 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Brackman G, Breyne K, De Rycke R, Vermote A, Van Nieuwerburgh F, Meyer E, Van Calenbergh S, Coenye T (2016) The quorum sensing inhibitor hamamelitannin increases antibiotic susceptibility of Staphylococcus aureus biofilms by affecting peptidoglycan biosynthesis and eDNA release. Sci Rep 6:20321.  https://doi.org/10.1038/srep20321 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Bronesky D, Wu Z, Marzi S, Walter P, Geissmann T, Moreau K, Vandenesch F, Caldelari I, Romby P (2016) Staphylococcus aureus RNAIII and its regulon link quorum sensing, stress responses, metabolic adaptation and regulation of virulence gene expression. J Clin Invest 70:299–316.  https://doi.org/10.1146/annurev-micro-102215-095708 CrossRefGoogle Scholar
  10. Bubeck Wardenburg J, Bae T, Otto M, Deleo FR, Schneewind O (2007) Poring over pores: alpha-hemolysin and Panton-valentine leukocidin in Staphylococcus aureus pneumonia. Nat Med 13:1405–1406.  https://doi.org/10.1038/nm1207-1405 CrossRefPubMedGoogle Scholar
  11. Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322.  https://doi.org/10.1126/science.284.5418.1318 CrossRefPubMedGoogle Scholar
  12. Defoirdt T, Brackman G, Coenye T (2013) Quorum sensing inhibitors: how strong is the evidence? Trends Microbiol 21:619–624.  https://doi.org/10.1016/j.tim.2013.09.006 CrossRefGoogle Scholar
  13. Dell’Acqua G, Giacometti A, Cirioni O, Ghiselli R, Saba V, Scalise G, Gov Y, Balaban N (2004) Suppression of drug-resistant staphylococcal infections by the quorum-sensing inhibitor RNAIII-inhibiting peptide. J Infect Dis 190:318–320.  https://doi.org/10.1086/386546 CrossRefPubMedGoogle Scholar
  14. Dhasmana N, Singh LK, Bhaduri A, Misra R, Singh Y (2014) Recent developments in anti-dotes against anthrax. Recent Pat Antiinfect Drug Discov 9:83–96CrossRefPubMedGoogle Scholar
  15. Elmore BO, Triplett KD, Hall PR (2015) Apolipoprotein B48, the structural component of chylomicrons, is sufficient to antagonize Staphylococcus aureus quorum-sensing. PLoS One 10:e0125027.  https://doi.org/10.1371/journal.pone.0125027 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Femling JK, West SD, Hauswald EK, Gresham HD, Hall PR (2013) Nosocomial infections after severe trauma are associated with lower apolipoproteins B and AII. J Trauma Acute Care Surg 74:1067–1073.  https://doi.org/10.1097/TA.0b013e3182826be0 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Geisinger E, George EA, Muir TW, Novick RP (2008) Identification of ligand specificity determinants in AgrC, the Staphylococcus aureus quorum-sensing receptor. J Biol Chem 283:8930–8938.  https://doi.org/10.1074/jbc.M710227200 CrossRefPubMedPubMedCentralGoogle Scholar
  18. George EA, Muir TW (2007) Molecular mechanisms of agr quorum sensing in virulent staphylococci. Chembiochem 8:847–855.  https://doi.org/10.1002/cbic.200700023 CrossRefPubMedGoogle Scholar
  19. George EA, Novick RP, Muir TW (2008) Cyclic peptide inhibitors of staphylococcal virulence prepared by Fmoc-based thiolactone peptide synthesis. J Am Chem Soc 130:4914–4924.  https://doi.org/10.1021/ja711126e CrossRefPubMedGoogle Scholar
  20. Giacometti A, Cirioni O, Gov Y, Ghiselli R, Del Prete MS, Mocchegiani F, Saba V, Orlando F, Scalise G, Balaban N, Dell’Acqua G (2003) RNA III inhibiting peptide inhibits in vivo biofilm formation by drug-resistant Staphylococcus aureus. Antimicrob Agents Chemother 47:1979–1983.  https://doi.org/10.1128/AAC.47.6.1979-1983.2003 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gordon RJ, Lowy FD (2008) Pathogenesis of methicillin-resistant Staphylococcus aureus infection. Clin Infect Dis 46:350–359.  https://doi.org/10.1086/533591 CrossRefGoogle Scholar
  22. Gov Y, Bitler A, Dell’Acqua G, Torres JV, Balaban N (2001) RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis: structure and function analysis. Peptides 22:1609–1620.  https://doi.org/10.1016/S0196-9781(01)00496-X CrossRefPubMedGoogle Scholar
  23. Gov Y, Borovok I, Korem M, Singh VK, Jayaswal RK, Wilkinson BJ, Rich SM, Balaban N (2004) Quorum sensing in staphylococci is regulated via phosphorylation of three conserved histidine residues. J Biol Chem 279:14665–14672.  https://doi.org/10.1074/jbc.M311106200 CrossRefPubMedGoogle Scholar
  24. Gui Z, Wang H, Ding T, Zhu W, Zhuang X, Chu W (2014) Azithromycin reduces the production of α-hemolysin and biofilm formation in Staphylococcus aureus. Indian J Microbiol 54:114–117.  https://doi.org/10.1007/s12088-013-0438-4 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Hall PR, Elmore BO, Spang CH, Alexander SM, Manifold-Wheeler BC, Castleman MJ, Daly SM, Peterson MM, Sully EK, Femling JK, Otto M, Horswill AR, Timmins GS, Gresham HD (2013) Nox2 modification of LDL is essential for optimal apolipoprotein B-mediated control of agr type III Staphylococcus aureus quorum-sensing. PLoS Pathog 9:e1003166.  https://doi.org/10.1371/journal.ppat.1003166 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Han R (2010) Plasma lipoproteins are important components of the immune system. Microbiol Immunol 54:246–253.  https://doi.org/10.1111/j.1348-0421.2010.00203.x CrossRefPubMedGoogle Scholar
  27. Huma N, Shankar P, Kushwah J, Bhushan A, Joshi J, Mukherjee T, Raju SC, Purohit HJ, Kalia VC (2011) Diversity and polymorphism in AHL-lactonase gene (aiiA) of Bacillus. J Microbiol Biotechnol 21:1001–1011.  https://doi.org/10.4014/jmb.1105.05056 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Jarraud S, Lyon GJ, Figueiredo AMS, Gerard L, Vandenesch F, Etienne J, Muir TW, Novick RP (2000) Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus. J Bacteriol 182:6517–6522.  https://doi.org/10.1128/JB.182.22.6517-6522.2000 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Ji G, Beavis R, Novick RP (1997) Bacterial interference caused by autoinducing peptide variants. Science 276:2027–2030.  https://doi.org/10.1126/science.276.5321.2027 CrossRefPubMedGoogle Scholar
  30. Johnson JG, Wang BY, Debelouchina GT, Novick RP, Muir TW (2015) Increasing AIP macrocycle size reveals key features of agr activation in Staphylococcus aureus. Chem Bio Chem 16:1093–1100.  https://doi.org/10.1002/cbic.201500006 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kalia VC (2014a) Microbes, antimicrobials and resistance: the battle goes on. Indian J Microbiol 54:1–2.  https://doi.org/10.1007/s12088-013-0443-7 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kalia VC (2014b) In search of versatile organisms for quorum-sensing inhibitors: acyl homoserine lactones (AHL)-acylase and AHL-lactonase. FEMS Microbiol Letts 359:143.  https://doi.org/10.1111/1574-6968.12585 CrossRefGoogle Scholar
  33. Kalia VC, Purohit HJ (2011) Quenching the quorum sensing system: potential antibacterial drug targets. Critical Rev Microbiol 37:121–140.  https://doi.org/10.3109/1040841X.2010.532479 CrossRefGoogle Scholar
  34. Kalia VC, Raju SC, Purohit HJ (2011) Genomic analysis reveals versatile organisms for quorum quenching enzymes: acyl-homoserine lactone-acylase and –lactonase. Open Microbiol J 5:1–13.  https://doi.org/10.2174/1874285801105010001 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kalia VC (2015) Microbes: the most friendly beings? In: Quorum sensing vs quorum quenching: a battle with no end in sight. Springer, New Delhi, pp 1–5.  http://dx.doi.org/10.1007/978-81-322-1982-8_1 Google Scholar
  36. Kattelmann KK, Hise M, Russell M, Charney P, Stokes M, Compher C (2006) Preliminary evidence for a medical nutrition therapy protocol: enteral feedings for critically ill patients. J Am Diet Assoc 106:1226–1241.  https://doi.org/10.1016/j.jada.2006.05.320 CrossRefPubMedGoogle Scholar
  37. Kaufmann GF, Sartorio R, Lee SY, Rogers CJ, Meijler MM, Moss JA, Clapham B, Brogan AP, Dickerson TJ, Janda KD (2005) Revisiting quorum sensing: discovery of additional chemical and biological functions for 3-oxo-N-acylhomoserine lactones. Proc Natl Acad Sci U S A 102:309–314.  https://doi.org/10.1073/pnas.0408639102 CrossRefPubMedGoogle Scholar
  38. Kiran MD, Adikesavan NV, Cirioni O, Giacometti A, Silvestri C, Scalise G, Ghiselli R, Saba V, Orlando F, Shoham M, Balaban N (2008) Discovery of a quorum-sensing inhibitor of drug resistant staphylococcal infections by structure-based virtual screening. Mol Pharmacol 73:1578–1586.  https://doi.org/10.1124/mol.107.044164 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Koenig RL, Ray JL, Maleki SJ, Smeltzer MS, Hurlburt BK (2004) Staphylococcus aureus AgrA binding to the RNAIII-agr regulatory region. J Bacteriol 186:7549–7555.  https://doi.org/10.1128/JB.186.22.7549-7555.2004 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Koul S, Kalia VC (2017) Multiplicity of quorum quenching enzymes: a potential mechanism to limit quorum sensing bacterial population. Indian J Microbiol 57:100–108.  https://doi.org/10.1007/s12088-016-0633-1 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Kumar P, Patel SKS, Lee J-K, Kalia VC (2013) Extending the limits of Bacillus for novel biotechnological applications. Biotechnol Adv 31(8):1543–1561CrossRefPubMedGoogle Scholar
  42. Kumar P, Koul S, Patel SKS, Lee JK, Kalia VC (2015) Heterologous expression of quorum sensing inhibitory genes in diverse organisms. In: Quorum sensing vs quorum quenching: a battle with no end in sight. Springer, New Delhi, pp 343–356.  http://dx.doi.org/10.1007/978-81-322-1982-8_28 Google Scholar
  43. Le KY, Otto M (2015) Quorum-sensing regulation in staphylococci-an overview. Front Microbiol 6:1174.  https://doi.org/10.3389/fmicb.2015.01174 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Leonard PG, Bezar IF, Sidote DJ, Stock AM (2012) Identification of a hydrophobic cleft in the LytTR domain of AgrA as a locus for small molecule interactions that inhibit DNA binding. Biochemistry 51:10035–10043.  https://doi.org/10.1021/bi3011785 CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3–26.  https://doi.org/10.1016/S0169-409X(00)00129-0 CrossRefPubMedGoogle Scholar
  46. Loughman JA, Fritz SA, Storch GA, Hunstad DA (2009) Virulence gene expression in human community acquired Staphylococcus aureus infection. J Infect Dis 199:294–301.  https://doi.org/10.1086/595982 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Lowy FD (1998) Staphylococcus aureus infections. N Engl J Med 339:520–532.  https://doi.org/10.1056/NEJM199808203390806 CrossRefPubMedGoogle Scholar
  48. Lyon GJ, Mayville P, Muir TW, Novick RP (2000) Rational design of a global inhibitor of the virulence response in Staphylococcus aureus, based in part on localization of the site of inhibition to the receptor-histidine kinase AgrC. Proc Natl Acad Sci U S A 97:13330–13335.  https://doi.org/10.1073/pnas.97.24.13330 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Lyon GJ, Wright JS, Muir TW, Novick RP (2002) Key determinants of receptor activation in the agr autoinducing peptides of Staphylococcus aureus. Biochemistry 41:10095–11104.  https://doi.org/10.1021/bi026049u CrossRefPubMedGoogle Scholar
  50. Mansson M, Nielsen A, Kjærulff L, Gotfredsen CH, Wietz M, Ingmer H, Gram L, Larsen TO (2011) Inhibition of virulence gene expression in Staphylococcus aureus by novel depsipeptides from a marine photobacterium. Mar Drugs 9:2537–2552.  https://doi.org/10.3390/md9122537 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Marr KA (2000) Staphylococcus aureus bacteremia in patients undergoing hemodialysis. Semin Dial 13:23–29.  https://doi.org/10.1046/j.1525-139x.2000.00009.x CrossRefPubMedGoogle Scholar
  52. Mayville P, Ji G, Beavis R, Yang H, Goger M, Novick RP, Muir TW (1999) Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. Proc Natl Acad Sci U S A 96:1218–1223.  https://doi.org/10.1073/pnas.96.4.1218 CrossRefPubMedPubMedCentralGoogle Scholar
  53. McDowell P, Affas Z, Reynolds C, Holden MT, Wood SJ, Saint S, Cockayne A, Hill PJ, Dodd CE, Bycroft BW, Chan WC, Williams P (2001) Structure, activity and evolution of the group I thiolactone peptide quorum-sensing system of Staphylococcus aureus. Mol Microbiol 41:503–512.  https://doi.org/10.1046/j.1365-2958.2001.02539.x CrossRefGoogle Scholar
  54. Murray EJ, Crowley RC, Truman A, Clarke SR, Cottam JA, Jadhav GP, Steele VR, O’Shea P, Lindholm C, Cockayne A, Chhabra SR, Chan WC, Williams P (2014) Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors. J Med Chem 57:2813–2819.  https://doi.org/10.1021/jm500215s CrossRefPubMedPubMedCentralGoogle Scholar
  55. Nielsen A, Månsson M, Bojer MS, Gram L, Larsen TO, Novick RP, Frees D, Frøkiær H, Ingmer H (2014) Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils. PLoS One 9:e84992.  https://doi.org/10.1371/journal.pone.0084992 CrossRefPubMedPubMedCentralGoogle Scholar
  56. Novick RP, Geisinger E (2008) Quorum sensing in staphylococci. Annu Rev Genet 42:541–564.  https://doi.org/10.1146/annurev.genet.42.110807.091640 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Qazi S, Middleton B, Muharram SH, Cockayne A, Hill P, O’Shea P, Chhabra SR, Cámara M, Williams P (2006) N-acylhomoserine lactones antagonize virulence gene expression and quorum sensing in Staphylococcus aureus. Infect Immun 74:910–919.  https://doi.org/10.1128/IAI.74.2.910–919.2006 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Sully EK, Malachowa N, Elmore BO, Alexander SM, Femling JK, Gray BM, DeLeo FR, Otto M, Cheung AL, Edwards BS, Sklar LA, Horswill AR, Hall PR, Gresham HD (2014) Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance. PLoS Pathog 10:e1004174.  https://doi.org/10.1371/journal.ppat.1004174 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Swift S, Downie JA, Whithead N, Barnard AML, Salmond GPC, Williams P (2001) Quorum sensing as a population density dependent determinant of bacterial physiology. Adv Microb Physiol 45:199–270.  https://doi.org/10.1016/S0065-2911(01)45005-3 CrossRefPubMedGoogle Scholar
  60. Tal-Gan Y, Ivancic M, Cornilescu G, Cornilescu CC, Blackwell HE (2013a) Structural characterization of native autoinducing peptides and abiotic analogues reveals key features essential for activation and inhibition of an AgrC quorum sensing receptor in Staphylococcus aureus. J Am Chem Soc 135:18436–18444.  https://doi.org/10.1021/ja407533e CrossRefPubMedGoogle Scholar
  61. Tal-Gan Y, Stacy DM, Foegen MK, Koenig DW, Blackwell HE (2013b) Highly potent inhibitors of quorum sensing in Staphylococcus aureus revealed through a systematic synthetic study of the group-III autoinducing peptide. J Am Chem Soc 135:7869–7882.  https://doi.org/10.1021/ja3112115 CrossRefPubMedGoogle Scholar
  62. Tal-Gan Y, Stacy DM, Blackwell HE (2014) N-methyl and peptoid scans of an autoinducing peptide reveal new structural features required for inhibition and activation of AgrC quorum sensing receptors in Staphylococcus aureus. Chem Commun 50:3000–3003.  https://doi.org/10.1039/c4cc00117f CrossRefGoogle Scholar
  63. Vasquez JK, Tal-Gan Y, Cornilescu G, Tyler KA, Blackwell HE (2017) Simplified AIP-II peptidomimetics are potent inhibitors of Staphylococcus aureus AgrC quorum sensing receptors. Chem Bio Chem 18:413–423.  https://doi.org/10.1002/cbic.201600516 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Vermote A, Brackman G, Risseeuw MDP, Vanhoutte B, Cos P, Van Hecke K, Breyne K, Meyer E, Coenye T, Van Calenbergh S (2016) Hamamelitannin analogues that modulate quorum sensing as potentiators of antibiotics against Staphylococcus aureus. Angew Chem Int Ed 55:6551–6555.  https://doi.org/10.1002/anie.201601973 CrossRefGoogle Scholar
  65. Vermote A, Brackman G, Risseeuw MDP, Cappoen D, Cos P, Coenye T, Van Calenbergh S (2017) Novel potentiators for vancomycin in the treatment of biofilm-related MRSA infections via a mix and match approach. ACS Med Chem Lett 8:38–42.  https://doi.org/10.1021/acsmedchemlett.6b00315 CrossRefPubMedGoogle Scholar
  66. Vuong C, Götz F, Otto M (2000) Construction and characterization of an agr deletion mutant of Staphylococcus epidermidis. Infect Immun 68:1048–1053.  https://doi.org/10.1128/IAI.68.3.1048-1053.2000 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Wadhwani SA, Shedbalkar UU, Singh R, Vashisth P, Pruthi V, Chopade BA (2016) Kinetics of synthesis of gold nanoparticles by Acinetobacter sp. SW30 isolated from environment. Indian J Microbiol 56:439–444.  https://doi.org/10.1007/s12088-016-0598-0 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Wang B, Muir TW (2016) Regulation of virulence in Staphylococcus aureus: molecular mechanisms and remaining puzzles. Cell Chem Biol 23:214–224.  https://doi.org/10.1016/j.chembiol.2016.01.004 CrossRefPubMedPubMedCentralGoogle Scholar
  69. Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, Kennedy AD, Dorward DW, Klebanoff SJ, Peschel A, DeLeo FR, Otto M (2007) Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 13:1510–1514.  https://doi.org/10.1038/nm1656 CrossRefPubMedGoogle Scholar
  70. Williams P (2002) Quorum sensing: an emerging target for antibacterial chemotherapy? Expert Opin Ther Targets 6:257–274.  https://doi.org/10.1517/14728222.6.3.257 CrossRefPubMedGoogle Scholar
  71. Wright JS 3rd, Lyon GJ, George EA, Muir TW, Novick RP (2004) Hydrophobic interactions drive ligand-receptor recognition for activation and inhibition of staphylococcal quorum sensing. Proc Natl Acad Sci U S A 101:16168–16173.  https://doi.org/10.1073/pnas.0404039101 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Wright GD, Sutherland AD (2007) New strategies for combating multidrug-resistant bacteria. Trends Mol Med 13:260–267.  https://doi.org/10.1016/j.molmed.2007.04.004 CrossRefPubMedGoogle Scholar
  73. Yarwood JM, Schlievert PM (2003) Quorum sensing in Staphylococcus infections. J Clin Invest 112:1620–1625.  https://doi.org/10.1172/JCI20442 CrossRefPubMedPubMedCentralGoogle Scholar
  74. Zapotoczna M, McCarthy H, Rudkin JK, O’Gara JP, O’Neill E (2015) An essential role for coagulase in Staphylococcus aureus biofilm development reveals new therapeutic possibilities for device-related infections. J Infect Dis 212:1883–1893.  https://doi.org/10.1093/infdis/jiv319 CrossRefPubMedGoogle Scholar
  75. Zapotoczna M, Murray EJ, Hogan S, O’Gara JP, Chhabra S, Chan WC, O’Neil E, Williams P (2017) 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus. J Antimicrob Chemother 72:744–753.  https://doi.org/10.1093/jac/dkw482 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Nishant Kumar
    • 1
    • 2
  • Hansita Gupta
    • 3
  • Neha Dhasmana
    • 1
    • 2
  • Yogendra Singh
    • 3
    • 2
  1. 1.Allergy and Infectious DiseasesCSIR – Institute of Genomics and Integrative BiologyDelhiIndia
  2. 2.Academy of Scientific & Innovative Research (AcSIR)New DelhiIndia
  3. 3.Department of ZoologyUniversity of DelhiDelhiIndia

Personalised recommendations