This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Pal, D. Articles by Samuelson, J. PubMed PubMed Citation Articles by Pal, D. Articles by Samuelson, J.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother. doi:10.1128/AAC.00909-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (NIMs)

Department of Biotechnology, Indian Institute of Technology, Kharagpur, West Bengal, India, 721302; Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts 02118

^* To whom correspondence should be addressed. Email: sudip{at}hijli.iitkgp.ernet.in.

	Abstract

Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we showed that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes, which are homologous to those that have nonsense mutations in metronidazole-resistant Helicobacter pylori. Entamoeba and Trichomonas also have nim genes, which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than NADPH of Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli. Conversely, recombinant NIMs of Entamoeba and Trichmonas confered very strong metronidazole resistance to transformed bacteria. The ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacteria-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.