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去铁酮与去铁胺对小肠结肠炎耶尔森菌生长和毒力影响的比较

Comparison of the effects of deferiprone versus deferoxamine on growth and virulence of Yersinia enterocolitica.

作者信息

Lesic Biliana, Foulon Jeannine, Carniel Elisabeth

机构信息

Laboratoire des Yersinia, Institut Pasteur, 75724 Paris Cedex 15, France.

出版信息

Antimicrob Agents Chemother. 2002 Jun;46(6):1741-5. doi: 10.1128/AAC.46.6.1741-1745.2002.

Abstract

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.

摘要

去铁胺是一种用于治疗铁过载患者的药物,它有促进人体全身性小肠结肠炎耶尔森菌感染的能力。本研究的目的是确定唯一具有口服活性的替代治疗药物去铁酮是否具有同样的可能性。当小肠结肠炎耶尔森菌IP864在缺铁的化学限定培养基中生长时,添加去铁胺可促进其生长,而不同浓度的去铁酮均未表现出这种活性。同样,在缺铁的琼脂平板上,各种小肠结肠炎耶尔森菌菌株能够以剂量依赖的方式在浸有去铁胺的纸圆盘周围生长,而在去铁酮圆盘周围未观察到生长。在小鼠感染实验模型中,用去铁胺预处理的小鼠中,菌株IP864的50%致死剂量(LD50)降低了超过5个对数单位,而去铁酮预处理对其没有影响。因此,与去铁胺不同,去铁酮在体外不会增强致病性小肠结肠炎耶尔森菌的生长,并且在小鼠感染模型中没有促进小肠结肠炎耶尔森菌败血症的可能性。因此,去铁酮可能是侵袭性小肠结肠炎耶尔森菌感染期间一种有用的替代铁螯合疗法。

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