Metronidazole and the Redox Biochemistry of Entamoeba histolytica

Metronidazole remains the gold standard drug for treatment for Entamoeba histolytica infections. In the introduction of this chapter, the drug is described: its history, its major uses, and some concerns raised about its genotoxicity in the past. Even a short introduction shows that the activity of metronidazole is closely linked with the redox metabolism of its target organisms. Thus, in the first section, the metabolism of E. histolytica under microaerophilic conditions is described. The second section reviews the thiol-containing antioxidant systems of E. histolytica in comparison to other organisms. The third part considers how E. histolytica can handle and inactivate molecular oxygen and more reactive oxygen and nitrogen species. In the fourth part, the activity of metronidazole is discussed in the light of the redox metabolism of E. histolytica. The fifth part addresses the prospects of metronidazole resistance, and the chapter ends with a final section on perspectives, where we stand, and some of the unresolved questions.