%0 Journal Article
%T Reconstruction of Sugar Metabolic Pathways of Giardia lamblia
%A Jian Han
%A Lesley J. Collins
%J International Journal of Proteomics
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/980829
%X Giardia lamblia is an ¡°important¡± pathogen of humans, but as a diplomonad excavate it is evolutionarily distant from other eukaryotes and relatively little is known about its core metabolic pathways. KEGG, the widely referenced site for providing information of metabolism, does not yet include many enzymes from Giardia species. Here we identify Giardia¡¯s core sugar metabolism using standard bioinformatic approaches. By comparing Giardia proteomes with known enzymes from other species, we have identified enzymes in the glycolysis pathway, as well as some enzymes involved in the TCA cycle and oxidative phosphorylation. However, the majority of enzymes from the latter two pathways were not identifiable, indicating the likely absence of these functionalities. We have also found enzymes from the Giardia glycolysis pathway that appear more similar to those from bacteria. Because these enzymes are different from those found in mammals, the host organisms for Giardia, we raise the possibility that these bacteria-like enzymes could be novel drug targets for treating Giardia infections. 1. Introduction Giardia lamblia is a major cause of human waterborne diarrheal disease, infecting an estimated 10% of the world¡¯s population during their lifetime [1]. Infection is by fecal-oral transmission and is initiated by ingestion of infectious cysts in contaminated water or through person-to-person contact. After excystation, flagellated trophozoites colonize the upper small intestine where they attach to the epithelial lining but do not invade the mucosa. Around 50% of Giardia infections are asymptomatic, in others the major symptoms of Giardia infection include diarrhea, with malabsorption, dehydration, weight loss, cognitive impairment in children, and chronic fatigue in adults as well as other symptoms [2]. One of the main drugs for treating Giardia infection is metronidazole (Mz) [3, 4]. However, Mz treatment fails in about 20% of patients [5] and there are other issues including developing resistance from Giardia [2]; moreover, Mz is inactive against Giardia cysts [6]. The discovery and development of new therapeutics are important to expand the arsenal for controlling parasitic infection. Typically a drug target is a key molecule involved in a metabolic or signalling pathway that is specific to a disease condition or pathology, or to the infectivity or survival of a microbial pathogen [7]. Since Giardia is a parasite with limited metabolic diversity, a better understanding of its metabolic pathways is important to the discovery of new drug targets. Although it has
%U http://www.hindawi.com/journals/ijpro/2012/980829/