Iron Increases Susceptibilities of Pseudomonas aeruginosa to Ofloxacin by Increasing the Permeability

  • Published : 2002.12.01

Abstract

Iron increased the susceptibilities of clinical isolates Pseudomonas aeruginosa to quinolones. In the presence of iron, increased susceptibilities to ofloxacin were observed in twenty-six out of thirty isolates and with no change in four isolates. In the case of norfloxacin, iran increased susceptibilities of twelve isolates but did not render any change in eighteen isolates. In the case of ciprofloxacin, iron decreased the MICs (Minimal Inhibitory Concentration) of twenty isolates, increased the MIC of one isolate, and did net change the MICs of nine isolates. To find out how iron increased susceptibility to ofloxacin, bacterial cells were grown in Muller Hinton (MH) media and succinate minimal media (SMM) to induce iran acquisition systems and the intracellular ofloxacin concentrations were assayed in the presence of iron. The addition of iron to the media decreased the MICs of cells whether they were grown in MH or SMM. Siderophores, carbonyl cyanide m-chlorophenylhydrazone (an inhibiter of proton motive force), and ouabain (an inhibitor of ATPase) did not decrease the effect of iron. Results suggested that the increase in the intracellular ofloxacin concentration by iron is accomplished not by decreasing the efflux but by increasing the of ofloxacin permeability.

Keywords

References

  1. Antimicrob. Agents Chemother v.41 Conservation of the multidrug resistance efflux gene oprM in Pseudomonas aerug-inosa Bianco,N.;S.Neshat;K.Poole
  2. Trends in Biochemical Sciences v.24 no.3 Bacterial solution to the iron-supply problem Braum,V.;H.Killmann https://doi.org/10.1016/S0968-0004(99)01359-6
  3. Antimicrob. Agents Chemother v.36 Salicylate-inducible antibiotic resistance in Pseudomonas cepacia associated with absence of a pore-forming outer membrane protein Burns,J.L.;D.K.Clark
  4. Antimicrob. Agents Chemother v.3 Factors influencing the accumulation of ciprofloxin in Pseudomonas aeruginosa. Celesk,R.A.;N.J.Robillard
  5. Antimicrob. Agents Chemother v.33 Chacterizqation of mechanisms of quinolone resistance in Pseudomonas aeruginosa strains isolated in vitro and in vivo during experimental endocarditis Chamverland,S.;A.S.Bayer;T.Schollaardt;S.A.Wong;L.E.Bryan
  6. Infect. Immun v.48 Siderophore activity of pyover-din for Pseudomonas aeruginosa Cox,C.D.;P.Adams
  7. J. Gen. Microbiol v.138 Siderophore-specific induction of iron uptake in Pseudomonas aeruginosa Gensberg,K.;K.Hughes;A.W.Smith
  8. Annual Review of Microbiology v.48 Microbial iron transport Guerinot,M.L. https://doi.org/10.1146/annurev.mi.48.100194.003523
  9. Antimicrob. Agents Chemother v.31 Mutations producing norfloxacin resistance in Pseudomonas aeruginosa Hirai,K.;S.Souza;T.Irikura;S.Iyobe;S.Mitsuhashi
  10. Antimicrob. Agents Chemother v.4 Differential selection of multidrug efflux systems by quinolones in Pseudomonas aeruginosa Kohler,T.;M.Michea-Hamzehpour;P.Plesiat;A.L.Kahr;J.c.Pechere
  11. Antimicrob. Agents Chemother v.38 Cloning and nucleotide sequence of Pseudomonas aeruginosa DNA gyrA gene from strain PAO1 and quinolone-resistant clinical isolates Kureishi,A.;J.M.Diver;B.Beckthold;T.Schollaardt;L.E.Bryan
  12. Archives of Pharmacal Research v.21 no.6 Ofloxacin resistance mechanism in PA150 and PA300-clinical isolates of Pseudomonas aeruginosa in Korea Lee,S.;Y.Lee https://doi.org/10.1007/BF02976755
  13. Antimicrob. Agents Chemother v.33 Outer membrane alteration in multiresistant mutants of Pseudomonas aeruginosa selected by ciprofloxaicn Legakis,N.J.;L.S.Tzouvelelkis;A.Makris;H.Kotsifaki
  14. Antimicrob. Agents Chemother v.36 Active efflux mechanisms for antimicrobial resistance Levy,S.B.
  15. Antimicrob. Agents Chemother v.39 Role of MexA-MexB-OprM in antibiotic efflux in Pseudomonas aeruginosa Li,X.;H.Nikaido;K.Poole
  16. Molecular Microbiology v.28 no.4 TonB-dependent iron acqusition:mechanisms of siderophore-mediated active transport Moeck,G.S.;J.W.Coulton https://doi.org/10.1046/j.1365-2958.1998.00817.x
  17. NCCLS document M100-S8 Performance standards for antimicrobial testing:eight informational supplements National Committee for Clinical Laboratory Standards
  18. J. Bacteriol v.153 Pseudomonas aeruginosa outer membrane permeability:isolation of a porin protein F-deficient mutant Nicas,T.I.;R.E.W.Hancock.
  19. Science v.264 no.5157 Prevention of drug access to bacterial targets:permeability barriers and active efflux Nikaido,H. https://doi.org/10.1126/science.8153625
  20. Current Opinion in Microbiology v.1 no.5 Multidrug antibiotic resistance and efflux Nikaido,H https://doi.org/10.1016/S1369-5274(98)80083-0
  21. Antimicrobial Agents and Chemotherapy v.44 no.7 Role of putative loops 2 and 3 in imipenem passage through the specific porin OprD of Pseudomonas aeruginosa Ochs,M.M.;M.P.Bains;R.E.W.Hancock https://doi.org/10.1128/AAC.44.7.1983-1985.2000
  22. Antimicrob. Agents Chemother v.32 Genetic and physiological characterization of ciprofloxacim resistance in Pseudomonas aeruginosa PAO Robillard,N.J.;A.L.Scarpa
  23. Analytical Biochemistry v.160 no.1 Universal chemical assay for the detection and determination of siderophores Schwyn,B.;J.B.Neilands https://doi.org/10.1016/0003-2697(87)90612-9
  24. Antimicrob. Agents Chemother v.37 Transient carbapenem resistance induced by salocylate in Pseudomonas aeruginosa associated with suppression of outer membrane protein D2 synthesis Sumita,Y.;M.Fukasawa
  25. Antimicrob. Agents Chemother v.39 DNA gyrase gyrA mutations in quinolone-resistant clinical isolates of Pseudomonas aeruginosa Yonezawa,M.;M.Takahata;N.Matsubara;Y.Watanabe;H.Narita
  26. Antimicrob. Agents Chemother v.38 Mechanism of high-level resistance to quinolones in urinary tract isolates of Pseudomonas aeruginosa Yoshida,T.;T.Muratani;S.Iyobe;S.Mitsuhashi
  27. Antimicrob. Agents Chemother v.42 Influence of TonB energy-coupling protein on efflux-mediated multidrug resistance in Pseudomonas aeruginosa Zhao,Q.;X.Z.Li;A.Mistry;R.Srikuma;L.Zhang;O.Lomovskaya;K.Poole
  28. Antimicrob. Agents Chemother v.43 In vivo emergence of multidrug-resistant mutants of Pseudinibas aeruginosa overexpressing the active efflux system MexA-MexB-OprM Ziha-zarifi,I.;C.Llanes;T.Kohler;J.C.Pechere;P.Plesiaf