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- Title
Effects of iron depletion on Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) and trophozoite growth: implications for antiamoebic therapy.
- Authors
Avelina Espinosa; George Perdrizet; Guillermo Paz-y-Miño C.; Regine Lanfranchi; Monichan Phay
- Abstract
Objectives The purpose of this study was to determine the mechanism by which iron chelation affects the trophozoite survival of Entamoeba histolytica. Fe2+ is a cofactor for E. histolytica alcohol dehydrogenase 2 (EhADH2), an essential bifunctional enzyme [alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] in the glycolytic pathway of E. histolytica. Methods We tested the effects of iron depletion on trophozoite growth, the kinetics of iron binding to EhADH2, and the activities of ADH and ALDH. Results Growth of E. histolytica trophozoites, and ADH and ALDH enzymatic activities were directly inhibited by iron chelation. Kinetics of iron binding to EhADH2 reveals the differential iron affinity of ADH (higher) and ALDH (lower). Conclusions This study demonstrates that iron chelation interrupts the completion of the fermentative pathway of E. histolytica by removing the metal cofactor indispensable for the structural and functional stability of EhADH2, thus affecting trophozoite survival. We propose that iron-starvation-based strategies could be used to treat amoebiasis.
- Subjects
CHELATION therapy; IRON in the body; TREATMENT effectiveness; AMEBIASIS treatment; ALCOHOL dehydrogenase; ENTAMOEBA histolytica; ALDEHYDE dehydrogenase; ENZYME kinetics
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2009, Vol 63, Issue 4, p675
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkp015