Comparison of the effects of deferiprone versus deferoxamine on growth and virulence of Yersinia enterocolitica.
Deferoxamine, a drug used to treat patients with iron overload, has the capacity to promote systemic Y. enterocolitica infections in humans. The aim of this study was to determine whether deferiprone, the only orally active alternative treatment, has the same potential. When Y. enterocolitica IP864 was grown in an iron-poor chemically defined medium, addition of deferoxamine promoted its growth, while various concentrations of deferiprone did not display this activity. Similarly, on iron-poor agar plates, various Y. enterocolitica strains were able to grow around paper disks impregnated with deferoxamine in a dose-dependent manner, while no growth was observed around the deferiprone disks. In a mouse experimental model of infection, the 50% lethal dose (LD(50)) of strain IP864 was decreased by more than 5 log units in mice pretreated with deferoxamine, while a deferiprone pretreatment did not affect it. Therefore, in contrast to deferoxamine, deferiprone does not enhance growth of pathogenic Y. enterocolitica in vitro and does not have the potential to promote Y. enterocolitica septicemia in a mouse model of infection. Deferiprone may thus represent a useful alternative iron-chelation therapy during invasive Y. enterocolitica infections.
Lesic
Biliana
B
Laboratoire des Yersinia, Institut Pasteur, 75724 Paris Cedex 15, France.
Foulon
Jeannine
J
Carniel
Elisabeth
E
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D003470:Culture Media; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008826:Microbial Sensitivity Tests; D011728:Pyridones / Q000494:pharmacology*; D015009:Yersinia Infections / Q000188:drug therapy / Q000382:microbiology; D015008:Yersinia enterocolitica / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity*
D002614:Chelating Agents; D003470:Culture Media; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D015082:2,2'-Dipyridyl; D003676:Deferoxamine