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Eukaryotic Cell, March 2005, p. 504-515, Vol. 4, No. 3
1535-9778/05/$08.00+0     doi:10.1128/EC.4.3.504-515.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Comparative Genomic Hybridizations of Entamoeba Strains Reveal Unique Genetic Fingerprints That Correlate with Virulence

Preetam H. Shah,1 Ryan C. MacFarlane,2 Dhruva Bhattacharya,2 John C. Matese,3,{dagger} Janos Demeter,3 Suzanne E. Stroup,4 and Upinder Singh1,2*

Division of Infectious Diseases, Department of Internal Medicine,1 Department of Microbiology and Immunology, Stanford University School of Medicine,2 Department of Genetics, Center for Clinical Sciences Research, Stanford University, Stanford, California,3 Department of Internal Medicine, University of Virginia, Charlottesville, Virginia4

Received 26 September 2004/ Accepted 21 December 2004

Variable phenotypes have been identified for Entamoeba species. Entamoeba histolytica is invasive and causes colitis and liver abscesses but only in ~10% of infected individuals; 90% remain asymptomatically colonized. Entamoeba dispar, a closely related species, is avirulent. To determine the extent of genetic diversity among Entamoeba isolates and potential genotype-phenotype correlations, we have developed an E. histolytica genomic DNA microarray and used it to genotype strains of E. histolytica and E. dispar. On the basis of the identification of divergent genetic loci, all strains had unique genetic fingerprints. Comparison of divergent genetic regions allowed us to distinguish between E. histolytica and E. dispar, identify novel genetic regions usable for strain and species typing, and identify a number of genes restricted to virulent strains. Among the four E. histolytica strains, a strain with attenuated virulence was the most divergent and phylogenetically distinct strain, raising the intriguing possibility that genetic subtypes of E. histolytica may be partially responsible for the observed variability in clinical outcomes. This microarray-based genotyping assay can readily be applied to the study of E. histolytica clinical isolates to determine genetic diversity and potential genotypic-phenotypic associations.

* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Diseases, S-141 Grant Building, 300 Pasteur Dr., Stanford, CA 94305. Phone: (650) 723-4045. Fax: (650) 724-3892. E-mail: usingh{at}stanford.edu.

{dagger} Present address: Lewis-Sigler Institute for Integrative Genomics,Princeton, NJ 08544.

Eukaryotic Cell, March 2005, p. 504-515, Vol. 4, No. 3
1535-9778/05/$08.00+0     doi:10.1128/EC.4.3.504-515.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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