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Plasmid mediated quinolone resistance

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Plasmid mediated quinolone resistance

  1. 1. Quinolones resistance (Strong When United, weak when divided.) BY SUSHMITA JHA.
  2. 2. Quinolones Discovered as byproduct of the synthesis of chloroquine Synthetic broad-spectrum antibacterial drugs
  3. 3. Nalidixic Acid Ciprofloxacin Levofloxacin Trovafloxacin Well Known Quinolone antibiotics
  4. 4. Target of the drug Bacterial enzymes DNA gyrase Topoisomerase IV
  5. 5. Commonly treated infections Gonorrhoea ,  Urinary tract infections, Respiratory tract infections,  Methicillin-susceptible Staphylococcus infections,  Gram-negative bacterial infections,  Gastrointestinal tract infections, Typhoid fever,  Nontyphoidal Salmonella gastroenteritis,
  6. 6. Mechanisms of quinolone resistance 1. Gyrase and Topoisomerase Gene Mutations 2. Alterations in Efflux 3. Cell Membrane Alternations 4. Plasmid-mediated Resistance ( pMG252)
  7. 7. Plasmid-mediated Resistance(pMG252) • Natural transferable plasmid. Qnr
  8. 8. qnrA,( was found to protect E. coli DNA gyrase from inhibition by ciprofloxacin.) qnrS1 (from Shigella flexneri 2b) qnrB1 (from K. pneumoniae) qnr gene:-
  9. 9. qnr ??? Present within a integron like environment upstream from qacEΔ1 and suI1. 218 Amino Acid protein – pentapeptide repeat family(homologous to McbG)
  10. 10. Experiment AIM The ability of qnr to reverse the gyrase activity by quinolones  qnr protection of Dna gyrase is propoRtional concentration. Dependence of Qnr protection on ciprofloxacin concentration
  11. 11. The ability of Qnr to reverse the gyrase activity by quinolones. Case 1:- 1 2 3 4 5 6 DNA Gyrase + + + + + Ciprofloxacin (.5µg/ml) + + + + Qnr ++ +
  12. 12. 1 2 3 4 5 6 7 8 9 10 DNA Gyrase + + + + + + + + + ciprofloxacin + + + + + + + + Qnr +++ + + + + + + Qnr protection of Dna gyrase is proportional to concentration . 96% 75% 31% No Protection Zone (less than 81 nM) Case 2:-
  13. 13. 1 2 3 4 5 6 7 8 9 10 DNA Gyrase + + + + + + + + + Qnr + + + + Ciprofloxacin + + + + + + + + Dependence of Qnr protection on Ciprofloxacin concentration Case 3:-
  14. 14. Effect of Qnr Gyrase Protection was inversly proportional to Concentration of ciprofloxacin Gyrase Protection was proportional to Concentration of qnr.
  15. 15.  The conserved domain of the gyrA N-terminus -quinolone resistance determining region (QRDR).  Ala51 –Val Ala67-Ser Asp86-Ala Gln106-his Distort the drug binging region Chromosomal point mutations enhances quinolones resistance :-
  16. 16. Mutation in chromosome(Gyrase mutation)
  17. 17. Alterations in Efflux • The multidrug efflux system AcrA-AcrB- TolC • mediator of quinolone efflux in E. coli • primary mechanism of fluoroquinolone resistance in Salmonella
  18. 18. Conclusion Quinolones resistant in bacteria can take place in following ways: 1.Mutation in Chromosome. 2 Alteration in the efflux 3.Change in OMPs and LPS 4 Plasmid mediated resistance results due to Qnr which can inhibit the drug action
  19. 19. All for 1 , 1 for All
  20. 20. Some Harsh Truth
  21. 21. SSC ma’am, Teachers, friends. I would like to thank:

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