Applied Microbiology and Biotechnology

, Volume 100, Issue 21, pp 9265–9281 | Cite as

Dithiazole thione derivative as competitive NorA efflux pump inhibitor to curtail multi drug resistant clinical isolate of MRSA in a zebrafish infection model

  • Rene Christena Lowrence
  • Thiagarajan Raman
  • Himesh V. Makala
  • Venkatasubramanian Ulaganathan
  • Selva Ganesan Subramaniapillai
  • Ashok Ayyappa Kuppuswamy
  • Anisha Mani
  • Sundaresan Chittoor Neelakantan
  • Saisubramanian NagarajanEmail author
Applied microbial and cell physiology


Multi drug resistant (MDR) pathogens pose a serious threat to public health since they can easily render most potent drugs ineffective. Efflux pump inhibitors (EPI) can be used to counter the MDR phenotypes arising due to increased efflux. In the present study, a series of dithiazole thione derivatives were synthesized and checked for its antibacterial and efflux pump inhibitory (EPI) activity. Among 10 dithiazole thione derivatives, real-time efflux studies revealed that seven compounds were potent EPIs relative to CCCP. Zebrafish toxicity studies identified four non-toxic putative EPIs. Both DTT3 and DTT9 perturbed membrane potential and DTT6 was haemolytic. Among DTT6 and DTT10, the latter was less toxic as evidenced by histopathology studies. Since DTT10 was non-haemolytic, did not affect the membrane potential, and was least toxic, it was chosen further for in vivo study, wherein DTT10 potentiated effect of ciprofloxacin against clinical strain of MRSA and reduced bacterial burden in muscle and skin tissue of infected zebrafish by ~ 1.7 and 2.5 log fold respectively. Gene expression profiling of major efflux transport proteins by qPCR revealed that clinical isolate of MRSA, in the absence of antibiotic, upregulated NorA, NorB and MepA pump, whereas it downregulates NorC and MgrA relative to wild-type strain of Staphylococcus aureus. In vitro studies with NorA mutant strains and substrate profiling revealed that at higher concentrations DTT10 is likely to function as a competitive inhibitor of NorA efflux protein in S. aureus, whereas at lower concentrations it might inhibit ciprofloxacin efflux through NorB and MepA as implied by docking studies. A novel non-toxic, non-haemolytic dithiazole thione derivative (DTT10) was identified as a potent competitive inhibitor of NorA efflux pump in S. aureus using in silico, in vitro and in vivo studies. This study also underscores the importance of using zebrafish infection model to screen and evaluate putative EPI for mitigating MDR strains of S. aureus.


Dithiazole thiones Efflux pump inhibitor MRSA MIC reversal Zebrafish infection Ciprofloxacin 



The authors sincerely thank TRR funding provided by management, SASTRA University to NS to carry out this work. TR would like to thank the Science and Engineering Research Board (SERB), Government of India, (SERB/F/1266/2012-13, dated 31st May 2012) for financial support. DST-FIST funding (Grant No SR/FST/ETI-331/2013) provided by DST, Govt of India to SCBT, SASTRA University, is gratefully acknowledged. Infrastructure facility (CRF) established through R&M funds (Grant No R&M/0021/SCBT-007/2012-13) of SASTRA to carry out this work is gratefully acknowledged. R&M grant provided to Microbiology Department by Management SASTRA University is gratefully acknowledged. Research fellowship provided by UGC to L.R.C.Maulana Azad National Fellowship, UGC, New Delhi, India (MANF-2012-13-CHR-WES-13462), is gratefully acknowledged.

Author contribution:

CNS synthesized the compounds, SSG helped in purification and characterization of the compounds; NS designed study, LRC carried out the biological part of study, TR and UV designed in vivo and in silico part of study, AM carried out fish toxicity assays; AA helped in design and interpretation of gene expression data, NS, TR and UV wrote the paper.

Compliance with ethical standards


This work is supported by TRR research grant to NS by SASTRA University; DST SERB Funding to TR (SERB/F/1266/2012-13, dated 31st May 2012) and DST-FIST funding (Grant No SR/FST/ETI-331/2013).

Conflict of interest

Author 1 declares no conflict of interest, author 2 declares no conflict of interest, author 3 declares no conflict of interest, author 4 declares no conflict of interest, author 5 declares no conflict of interest, author 6 declares no conflict of interest, author 7 declares no conflict of interest, author 8 declares no conflict of interest and author 9 declares no conflict of interest.

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

253_2016_7759_MOESM1_ESM.pdf (3.4 mb)
ESM 1 Supporting information (PDF 3517 kb)


  1. Adamson DH, Krikstopaityte V, Coote PJ (2015) Enhanced efficacy of putative efflux pump inhibitor/antibiotic combination treatments versus MDR strains of Pseudomonas aeruginosa in a Galleria mellonella in vivo infection model. J Antimicrob Chemother 70(8):2271–8. doi: 10.1093/jac/dkv111 CrossRefPubMedGoogle Scholar
  2. Andrews JM (2001) Determination of minimum inhibitory concentrations. J Antimicrob Chemother 48(Suppl 1):5–16CrossRefPubMedGoogle Scholar
  3. Appelbaum PC (2006) The emergence of vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. Clin Microbiol Infect 12(Suppl 1):16–23. doi: 10.1111/j.1469-0691.2006.01344.x CrossRefPubMedGoogle Scholar
  4. Argentine JA, James AA (1995) Characterization of a salivary gland-specific esterase in the vector mosquito, Aedes aegypti. Insect Biochem Mol Biol 25(5):621–30CrossRefPubMedGoogle Scholar
  5. Asaithampi G, Lowrence RC, Himesh MVS, Ulaganathan V, Raman T, Venkatabalasubramanian S, Kabilan K, Nagarajan S, Subramaniapillai SG (2016) Identification of benzochromene derivatives as a highly specific NorA efflux pump inhibitor to mitigate the drug resistant strains of S. aureus.  RSC Adv 6 (36):30258–30267. doi: 10.1039/C6RA01981A
  6. Astashkina A, Mann B, Grainger DW (2012) A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity. Pharmacol Ther 134(1):82–106. doi: 10.1016/j.pharmthera.2012.01.001S0163-7258(12)00002-2 CrossRefPubMedGoogle Scholar
  7. Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ (2015) Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol 13(1):42–51. doi: 10.1038/nrmicro3380 CrossRefPubMedGoogle Scholar
  8. Blanchard C, Barnett P, Perlmutter J, Dunman PM (2014) Identification of Acinetobacter baumannii serum-associated antibiotic efflux pump inhibitors. Antimicrob Agents Chemother 58(11):6360–70, doi: 10.1128/AAC.03535-14
  9. Brenwald NP, Gill MJ, Wise R (1998) Prevalence of a putative efflux mechanism among fluoroquinolone-resistant clinical isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother 42(8):2032–5PubMedPubMedCentralGoogle Scholar
  10. Costa SS, Falcao C, Viveiros M, Machado D, Martins M, Melo-Cristino J, Amaral L, Couto T (2011) Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus Google Scholar
  11. Ding Y, Onodera Y, Lee JC, Hooper DC (2008) NorB, an efflux pump in Staphylococcus aureus strain MW2, contributes to bacterial fitness in abscesses. J Bacteriol 190(21):7123–9. doi: 10.1128/JB.00655-08 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Dong Y, Zhao X, Kreiswirth BN, Drlica K (2000) Mutant prevention concentration as a measure of antibiotic potency: studies with clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 44(9):2581–4Google Scholar
  13. Edman P (1949) A method for the determination of amino acid sequence in peptides. ADTTh Biochem 22(3):475Google Scholar
  14. Evangelista Sde S, de Oliveira AC (2015) Community-acquired methicillin-resistant Staphylococcus aureus: a global problem. Rev Bras Enferm 68(1):128–35. doi: 10.1590/0034-7167.2015680119pS0034-71672015000100136, 136-43PubMedGoogle Scholar
  15. Fontaine F, Hequet A, Voisin-Chiret AS, Bouillon A, Lesnard A, Cresteil T, Jolivalt C, Rault S (2014) First identification of boronic species as novel potential inhibitors of the Staphylococcus aureus NorA efflux pump. J Med Chem 57(6):2536–48. doi: 10.1021/jm401808n CrossRefPubMedGoogle Scholar
  16. Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC, Mainz DT (2006) Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 49(21):6177–96. doi: 10.1021/jm051256o CrossRefPubMedGoogle Scholar
  17. Gupta A, Mishra P, Kashaw SK, Jatav V (2008) Synthesis, anticonvulsant, antimicrobial and analgesic activity of novel 1,2,4-dithiazoles. Indian J Pharm Sci 70(4):535–8. doi: 10.4103/0250-474X.44614 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Hequet A, BuDTThak ON, Jeanty M, Guinchard X, Le Pihive E, Maigre L, Bouhours P, Schneider D, Maurin M, Paris JM, Denis JN, Jolivalt C (2014) 1-(1H-indol-3-yl)ethanamine derivatives as potent Staphylococcus aureus NorA efflux pump inhibitors. ChemMedChem 9(7):1534–45. doi: 10.1002/cmdc.201400042 CrossRefPubMedGoogle Scholar
  19. Huet AA, Raygada JL, Mendiratta K, Seo SM, Kaatz GW (2008) Multidrug efflux pump overexpression in Staphylococcus aureus after single and multiple in vitro exposures to biocides and dyes. Microbiology 154(Pt 10):3144–53. doi: 10.1099/mic.0.2008/021188-0154/10/3144 CrossRefPubMedGoogle Scholar
  20. Kalia NP, Mahajan P, Mehra R, Nargotra A, Sharma JP, Koul S, Khan IA (2012) Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus. J Antimicrob Chemother 67(10):2401–8. doi: 10.1093/jac/dks232 CrossRefPubMedGoogle Scholar
  21. Kollef MH (2007) Limitations of vancomycin in the management of resistant staphylococcal infections. Clin Infect Dis 45(Suppl 3):S191–5. doi: 10.1086/519470 CrossRefPubMedGoogle Scholar
  22. Kosmidis C, Schindler BD, Jacinto PL, Patel D, Bains K, Seo SM, Kaatz GW (2012) Expression of multidrug resistance efflux pump genes in clinical and environmental isolates of Staphylococcus aureus. Int J Antimicrob Agents 40(3):204–9. doi: 10.1016/j.ijantimicag.2012.04.014S0924-8579(12)00184-7 CrossRefPubMedGoogle Scholar
  23. Kumar A, Khan IA, Koul S, Koul JL, Taneja SC, Ali I, Ali F, Sharma S, Mirza ZM, Kumar M, Sangwan PL, Gupta P, Thota N, Qazi GN (2008) Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus. J Antimicrob Chemother 61(6):1270–6. doi: 10.1093/jac/dkn088 CrossRefPubMedGoogle Scholar
  24. Lawson AJ, Meloy CR (1973) Derivatives of 5-amino-1,2,4-dithiazole-3-thione. 5(4):465-470Google Scholar
  25. Lin B, Chen S, Cao Z, Lin Y, Mo D, Zhang H, Gu J, Dong M, Liu Z, Xu A (2007) Acute phase response in zebrafish upon Aeromonas salmonicida and Staphylococcus aureus infection: striking similarities and obvious differences with mammals. Mol Immunol 44(4):295–301. doi: 10.1016/j.molimm.2006.03.001 CrossRefPubMedGoogle Scholar
  26. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schaberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, Lewis K (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517(7535):455–9. doi: 10.1038/nature14098 CrossRefPubMedGoogle Scholar
  27. Louw GE, Warren RM, Gey van Pittius NC, Leon R, Jimenez A, Hernandez-Pando R, McEvoy CR, Grobbelaar M, Murray M, van Helden PD, Victor TC (2011) Rifampicin reduces susceptibility to ofloxacin in rifampicin-resistant Mycobacterium tuberculosis through efflux. Am J Respir Crit Care Med 184(2):269–76. doi: 10.1164/DTTcm.201011-1924OC
  28. Christena LR, Subramaniam S, Vidhyalakshmi M, Mahadevan V, Sivasubramanian A, Nagarajan S (2015a) Dual role of pinostrobin-a flavonoid nutraceutical as an efflux pump inhibitor and antibiofilm agent to mitigate food borne pathogens. Rsc Advances 5(76):61881–61887. doi: 10.1039/C5RA07165H CrossRefGoogle Scholar
  29. Christena LR, Mangalagowri V, Pradheeba P, Ahmed KBA, Shalini BIS, Vidyalakshmi M, Anbazhagana V, Subramanian NS (2015b) Copper nanoparticles as an efflux pump inhibitor to tackle drug resistant bacteria. Rsc Advances 5(17):12899–12909. doi: 10.1039/C4RA15382K CrossRefGoogle Scholar
  30. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–75PubMedGoogle Scholar
  31. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18(3):268–81. doi: 10.1111/j.1469-0691.2011.03570.xS1198-743X(14)61632-3 CrossRefPubMedGoogle Scholar
  32. Maiti R, Van Domselaar GH, Zhang H, Wishart DS (2004) SuperPose: a simple server for sophisticated structural superposition. Nucleic Acids ReseaDTTh 32(Web Server issue):W590–W594. doi: 10.1093/nar/gkh477 CrossRefGoogle Scholar
  33. Martins M, Viveiros M, Couto I, Costa SS, Pacheco T, Fanning S, Pages JM, Amaral L (2011) Identification of efflux pump-mediated multidrug-resistant bacteria by the ethidium bromide-agar cartwheel method. In vivo (Athens, Greece) 25(2):171–8Google Scholar
  34. Mathers AJ, Peirano G, Pitout JD (2015) The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae. Clin Microbiol Rev 28(3):565–91. doi: 10.1128/CMR.00116-1428/3/565
  35. McAleese F, Petersen P, Ruzin A, Dunman PM, Murphy E, Projan SJ, Bradford PA (2005) A novel MATE family efflux pump contributes to the reduced susceptibility of laboratory-derived Staphylococcus aureus mutants to tigecycline. Antimicrob Agents Chemother 49(5):1865–71. doi: 10.1128/AAC.49.5.1865-1871.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  36. McHugh CG, Riley LW (2004) Risk factors and costs associated with methicillin-resistant Staphylococcus aureus bloodstream infections. Infect Control Hosp Epidemiol 25(5):425–30. doi: 10.1086/502417 CrossRefPubMedGoogle Scholar
  37. Merli M, Lucidi C, Di Gregorio V, Falcone M, Giannelli V, Lattanzi B, Giusto M, Ceccarelli G, FaDTTomeni A, Riggio O, Venditti M (2015) The spread of multi drug resistant infections is leading to an increase in the empirical antibiotic treatment failure in cirrhosis: a prospective survey. PLoS One 10(5):e0127448. doi: 10.1371/journal.pone.0127448PONE-D-14-38195 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Mohammad H, Reddy PV, Monteleone D, Mayhoub AS, Cushman M, Hammac GK, Seleem MN (2015) Antibacterial characterization of novel synthetic thiazole compounds against methicillin-resistant Staphylococcus pseudintermedius. PLoS One 10(6):e0130385. doi: 10.1371/journal.pone.0130385PONE-D-15-05317 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Munita JM, Bayer AS, Arias CA (2015) Evolving resistance among gram-positive pathogens. Clin Infect Dis 61(Suppl 2):S48–57. doi: 10.1093/cid/civ523 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Neely MN, Pfeifer JD, Caparon M (2002) Streptococcus-zebrafish model of bacterial pathogenesis. Infect Immun 70(7):3904–14CrossRefPubMedPubMedCentralGoogle Scholar
  41. Nelson MU, Bizzarro MJ, Baltimore RS, Dembry LM, Gallagher PG (2015) Clinical and molecular epidemiology of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit in the decade following implementation of an active detection and isolation program. J Clin Microbiol 53(8):2492–501. doi: 10.1128/JCM.00470-15 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Neyfakh AA, Borsch CM, Kaatz GW (1993) Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a multidrug efflux transporter. Antimicrob Agents Chemother 37(1):128–9CrossRefPubMedPubMedCentralGoogle Scholar
  43. Nikaido H (2009) Multidrug resistance in bacteria. Annu Rev Biochem 78:119–46. doi: 10.1146/annurev.biochem.78.082907.145923 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Nishino K, Nikaido E, Yamaguchi A (2009) Regulation and physiological function of multidrug efflux pumps in Escherichia coli and Salmonella. Biochim Biophys Acta 1794(5):834–43. doi: 10.1016/j.bbapap.2009.02.002S1570-9639(09)00026-0 CrossRefPubMedGoogle Scholar
  45. Niven GW, Mulholland F (1998) Cell membrane integrity and lysis in Lactococcus lactis: the detection of a population of permeable cells in post-logarithmic phase cultures. J Appl Microbiol 84(1):90–6CrossRefPubMedGoogle Scholar
  46. Pfeifer HJ, Greenblatt DK, Koch-Wester J (1976) Clinical toxicity of reserpine in hospitalized patients: a report from the Boston Collaborative Drug Surveillance Program. Am J Med Sci 271(3):269–76CrossRefPubMedGoogle Scholar
  47. Piddock LJ (2006) Multidrug-resistance efflux pumps—not just for resistance. Nat Rev Microbiol 4(8):629–36CrossRefPubMedGoogle Scholar
  48. Piddock LJ (2014) Understanding the basis of antibiotic resistance: a platform for drug discovery. Microbiology 160(Pt 11):2366–73. doi: 10.1099/mic.0.082412-0 CrossRefPubMedGoogle Scholar
  49. Rio DC (2015) Denaturation and electrophoresis of RNA with formaldehyde. Cold Spring Harb Protoc . doi: 10.1101/pdb.prot080994 Google Scholar
  50. Sabatini S, Gosetto F, Iraci N, Barreca ML, Massari S, Sancineto L, Manfroni G, Tabarrini O, Dimovska M, Kaatz GW, Cecchetti V (2013) Re-evolution of the 2-phenylquinolines: ligand-based design, synthesis, and biological evaluation of a potent new class of Staphylococcus aureus NorA efflux pump inhibitors to combat antimicrobial resistance. J Med Chem 56(12):4975–89. doi: 10.1021/jm400262a CrossRefPubMedGoogle Scholar
  51. Sannasiddappa TH, Hood GA, Hanson KJ, Costabile A, Gibson GR, Clarke SR (2015) Staphylococcus aureus MnhF mediates cholate efflux and facilitates survival under human colonic conditions. Infect Immun 83(6):2350–7. doi: 10.1128/IAI.00238-15 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Sarkissian EJ, Gans I, Gunderson MA, Myers SH, Spiegel DA, Flynn JM (2015) Community-acquired methicillin-resistant Staphylococcus aureus musculoskeletal infections: emerging trends over the past decade. J Pediatr Orthop. doi: 10.1097/BPO.0000000000000439 PubMedGoogle Scholar
  53. Sastry GM, Adzhigirey M, Day T, Annabhimoju R, Sherman W (2013) Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 27(3):221–34. doi: 10.1007/s10822-013-9644-8 CrossRefPubMedGoogle Scholar
  54. Sato T, Yokota S, Okubo T, Ishihara K, Ueno H, Muramatsu Y, Fujii N, Tamura Y (2013) Contribution of the AcrAB-TolC efflux pump to high-level fluoroquinolone resistance in Escherichia coli isolated from dogs and humans. J Vet Med Sci 75(4):407–14CrossRefPubMedGoogle Scholar
  55. Schindler BD, Jacinto P, Kaatz GW (2013) Inhibition of drug efflux pumps in Staphylococcus aureus: current status of potentiating existing antibiotics. Future Microbiol 8(4):491–507. doi: 10.2217/fmb.13.16 CrossRefPubMedGoogle Scholar
  56. Schrödinger (2010). Maestro,V9.3 Schrödinger LLC, New York Google Scholar
  57. Selter R, Considine WJ (1970) Basicity of isoperthiocyanic acid. J Org Chem 35(5):1665–1666Google Scholar
  58. Silverman JA, Perlmutter NG, Shapiro HM (2003) Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrob Agents Chemother 47(8):2538–44CrossRefPubMedPubMedCentralGoogle Scholar
  59. Srivastava P, Singh A (2014) Potential effects of agricultural fungicide (Mancozeb) on fish Clarias batrachus. Res J Biol Sci 9:129–134Google Scholar
  60. Sun J, Deng Z, Yan A (2014) Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun 453(2):254–67. doi: 10.1016/j.bbDTT.2014.05.090S0006-291X(14)00971-1 CrossRefPubMedGoogle Scholar
  61. Thaden JT, Ericson JE, Cross H, Bergin SP, Messina JA, Fowler VG Jr, Benjamin DK Jr, Clark RH, Hornik CP, Smith PB (2015) Survival benefit of empirical therapy for Staphylococcus aureus bloodstream infections in infants. Pediatr Infect Dis J. doi: 10.1097/INF.0000000000000850 Google Scholar
  62. Tillotson GS, Theriault N (2013) New and alternative approaches to tackling antibiotic resistance. F1000Prime Rep 5:51 doi: 10.12703/P5-51
  63. Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG Jr (2015) Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 28(3):603–61. doi: 10.1128/CMR.00134-1428/3/603 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Truong-Bolduc QC, Bolduc GR, Medeiros H, Vyas JM, Wang Y, Hooper DC (2015) Role of tet38 efflux pump in Staphylococcus aureus internalization and survival in epithelial cells. Infec Immun. doi: 10.1128/IAI.00723-15 Google Scholar
  65. Truong-Bolduc QC, Hsing LC, Villet R, Bolduc GR, Estabrooks Z, Taguezem GF, Hooper DC (2012) Reduced aeration effects the expression of the NorB efflux pump of Staphylococcus aureus by post translation modification of MgrA. J Bacteriol 1823-1834Google Scholar
  66. Wang SH, Hines L, van Balen J, Mediavilla JR, Pan X, Hoet AE, Kreiswirth BN, Pancholi P, Stevenson KB (2015) Molecular and clinical characteristics of hospital and community onset methicillin-resistant Staphylococcus aureus strains associated with bloodstream infections. J Clin Microbiol 53(5):1599–608. doi: 10.1128/JCM.03147-14 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Westerfield M (1995) The zebrafish book: guide for the laboratory use of zebrafish (Danio rerio), 3rd edn. University of Oregon Press, EugeneGoogle Scholar
  68. Wu S, Zhang Y (2008) MUSTER: improving protein sequence profile–profile alignments by using multiple sources of structure information. Proteins 72(2):547–556. doi: 10.1002/prot.21945

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Rene Christena Lowrence
    • 1
    • 3
  • Thiagarajan Raman
    • 1
    • 3
  • Himesh V. Makala
    • 1
  • Venkatasubramanian Ulaganathan
    • 1
  • Selva Ganesan Subramaniapillai
    • 1
  • Ashok Ayyappa Kuppuswamy
    • 1
  • Anisha Mani
    • 1
  • Sundaresan Chittoor Neelakantan
    • 2
  • Saisubramanian Nagarajan
    • 1
    • 3
    Email author
  1. 1.School of Chemical and BiotechnologySASTRA UniversityThanjavurIndia
  2. 2.Department of ChemistrySri Sathya Sai Institute of Higher LearningBengaluruIndia
  3. 3.Centre for Research in Infectious Diseases (CRID), School of Chemical & BiotechnologySASTRA UniversityThanjavurIndia

Personalised recommendations