This presentation contains detail informat

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

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)

8. Plasmid-mediated Resistance(pMG252)
• Natural transferable
plasmid.
Qnr

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 :-

17. Mutation in chromosome(Gyrase mutation)

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

21. Some Harsh Truth

22. SSC ma’am,
Teachers, friends.
I would like to thank: