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Quinolones resistance
(Strong When United,
weak when divided.)
BY
SUSHMITA JHA.
Quinolones
Discovered as byproduct of the
synthesis of chloroquine
Synthetic
broad-spectrum
antibacterial drugs
Nalidixic Acid Ciprofloxacin
Levofloxacin Trovafloxacin
Well Known Quinolone antibiotics
Target of the drug
Bacterial enzymes
DNA gyrase
Topoisomerase IV
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,
Mechanisms of quinolone resistance
1. Gyrase and
Topoisomerase Gene
Mutations
2. Alterations in Efflux
3. Cell Membrane
Alternations
4. Plasmid-mediated
Resistance ( pMG252)
Plasmid-mediated Resistance(pMG252)
• Natural transferable
plasmid.
Qnr
qnrA,( was found to protect E. coli DNA gyrase
from inhibition by ciprofloxacin.)
qnrS1 (from Shigella flexneri 2b)
qnrB1 (from K. pneumoniae)
qnr gene:-
qnr ???
Present within a integron like environment upstream from qacEΔ1 and
suI1.
218 Amino Acid protein –
pentapeptide repeat
family(homologous to
McbG)
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
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 ++ +
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:-
1 2 3 4 5 6 7 8 9 10
DNA Gyrase + + + + + + + + +
Qnr + + + +
Ciprofloxacin + + + + + + + +
Dependence of Qnr protection on
Ciprofloxacin concentration
Case 3:-
Effect of Qnr
Gyrase
Protection was
inversly
proportional to
Concentration of
ciprofloxacin
Gyrase
Protection was
proportional to
Concentration of
qnr.
 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 :-
Mutation in chromosome(Gyrase mutation)
Alterations in Efflux
• The multidrug efflux system AcrA-AcrB-
TolC
• mediator of quinolone efflux in E. coli
• primary mechanism of fluoroquinolone
resistance in Salmonella
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
All for 1 ,
1 for All
Some Harsh Truth
SSC ma’am,
Teachers, friends.
I would like to thank:
Plasmid mediated quinolone resistance

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Plasmid mediated quinolone resistance

  • 1. Quinolones resistance (Strong When United, weak when divided.) BY SUSHMITA JHA.
  • 2. Quinolones Discovered as byproduct of the synthesis of chloroquine Synthetic broad-spectrum antibacterial drugs
  • 3. Nalidixic Acid Ciprofloxacin Levofloxacin Trovafloxacin Well Known Quinolone antibiotics
  • 4. Target of the drug Bacterial enzymes DNA gyrase Topoisomerase IV
  • 5.
  • 6. 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,
  • 7. Mechanisms of quinolone resistance 1. Gyrase and Topoisomerase Gene Mutations 2. Alterations in Efflux 3. Cell Membrane Alternations 4. Plasmid-mediated Resistance ( pMG252)
  • 9. qnrA,( was found to protect E. coli DNA gyrase from inhibition by ciprofloxacin.) qnrS1 (from Shigella flexneri 2b) qnrB1 (from K. pneumoniae) qnr gene:-
  • 10. qnr ??? Present within a integron like environment upstream from qacEΔ1 and suI1. 218 Amino Acid protein – pentapeptide repeat family(homologous to McbG)
  • 11. 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
  • 12. 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 ++ +
  • 13. 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:-
  • 14. 1 2 3 4 5 6 7 8 9 10 DNA Gyrase + + + + + + + + + Qnr + + + + Ciprofloxacin + + + + + + + + Dependence of Qnr protection on Ciprofloxacin concentration Case 3:-
  • 15. Effect of Qnr Gyrase Protection was inversly proportional to Concentration of ciprofloxacin Gyrase Protection was proportional to Concentration of qnr.
  • 16.  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 :-
  • 18. Alterations in Efflux • The multidrug efflux system AcrA-AcrB- TolC • mediator of quinolone efflux in E. coli • primary mechanism of fluoroquinolone resistance in Salmonella
  • 19. 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
  • 20. All for 1 , 1 for All
  • 22. SSC ma’am, Teachers, friends. I would like to thank: