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JAC Advance Access originally published online on February 13, 2009
Journal of Antimicrobial Chemotherapy 2009 63(4):675-678; doi:10.1093/jac/dkp015
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Effects of iron depletion on Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) and trophozoite growth: implications for antiamoebic therapy

Avelina Espinosa1,*, George Perdrizet1, Guillermo Paz-y-Miño C.2, Regine Lanfranchi1 and Monichan Phay1

1 Department of Biology, Roger Williams University, One Old Ferry Road, Bristol, RI 02809, USA 2 Department of Biology, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, MA 02747-2300, USA

Received 13 November 2008; returned 11 December 2008; revised 31 December 2008; accepted 10 January 2009

* Corresponding author. Tel: +1-401-254-3137; Fax: +1-401-254-3310; E-mail: aespinosa{at}rwu.edu

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.

Keywords: AdhE , enzyme inhibition , E. histolytica


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