Effects of iron depletion on Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) and trophozoite growth: implications for antiamoebic therapy.
OBJECTIVE
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.
Espinosa
Avelina
A
Department of Biology, Roger Williams University, One Old Ferry Road, Bristol, RI 02809, USA. aespinosa@rwu.edu
Perdrizet
George
G
Paz-Y-Miño C
Guillermo
G
Lanfranchi
Regine
R
Phay
Monichan
M
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D004748:Entamoeba histolytica / Q000201:enzymology* / Q000254:growth & development* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D050296:Microbial Viability; D011485:Protein Binding; D053058:Trophozoites / Q000201:enzymology* / Q000254:growth & development* / Q000378:metabolism
D007502:Iron Chelating Agents; D007501:Iron; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase