Summary
The response to fosmidomycin of four strains ofEscherichia coli was studied in anin vitro model of the treatment of bacterial cystitis. Three susceptible strains ofE. coli responded well to relatively low concentrations of fosmidomycin: doses achieving peak concentrations of 50 or 250 mg/l suppressed bacterial growth for 13 h or more; however, when the surviving bacteria were challenged with a second dose, a reduced response was observed. When a fully resistant strain was exposed to fosmidomycin, bacterial growth was also suppressed for 13 h or more, even when the peak concentration achieved was below the conventionally determined minimum inhibitory concentration. Resistant variants which emerged after exposure to fosmidomycin were also resistant to fosfomycin in the absence of the potentiating agent, glucose-6-phosphate. In the presence of glucose-6-phosphate, complete (or partial) susceptibility to fosmidomycin and fosfomycin was retained by three of the four strains. These results suggest that fosmidomycin and fosfomycin are transported intoE. coli by a similar mechanism, and that deletion of the hexose phosphate transport system does not occur following exposure to fosmidomycin in the absence of glucose-6-phosphate.
Zusammenfassung
In einemIn vitro-Modell zur Behandlung der bakteriellen Zystitis wurden vier Stämme vonEscherichia coli auf ihr Ansprechen auf Fosmidomycin geprüft. Drei empfindliche Stämme vonE. coli sprachen gut auf relativ niedrige Konzentrationen von Fosmidomycin an: Dosen, mit denen Spitzenkonzentrationen von 50 oder 250 mg/l erreicht wurden, unterdrückten das Bakterienwachstum über 13 Stunden oder länger; wenn die überlebenden Bakterien jedoch mit einer zweiten Dosis angegriffen wurden, war eine verminderte Antwort festzustellen. Bei Exposition eines vollkommen resistenten Stammes gegenüber Fosmidomycin wurde das Bakterienwachstum ebenfalls für 13 Stunden und länger unterdrückt, auch dann, wenn die erreichte Spitzenkonzentration unter der mit konventionellen Methoden bestimmten minimalen Hemmkonzentration lag. Resistente Varianten, die nach Exposition gegenüber Fosmidomycin auftraten, waren in Abwesenheit des Wirkfaktors Glukose-6-Phosphat auch gegen Fosfomycin resistent. In Anwesenheit von Glukose-6-Phosphat behielten drei der vier Stämme ihre vollständige (oder partielle) Empfindlichkeit gegenüber Fosmidomycin und Fosfomycin. Aus den Ergebnissen läßt sich ein ähnlicher Transportmechanismus für Fosmidomycin und Fosfomycin inE. coli-Zellen ableiten; außerdem ist anzunehmen, daß die Aufhebung des Hexosephosphat-Transportsystems nach Exposition gegenüber Fosmidomycin in Abwesenheit von Glukose-6-Phosphat nicht stattfindet.
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Kanimoto, Y., Greenwood, D. Activity of fosmidomycin in an in vitro model of the treatment of bacterial cystitis. Infection 15, 465–468 (1987). https://doi.org/10.1007/BF01647239
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DOI: https://doi.org/10.1007/BF01647239