Anti-infectives targeting the isoprenoid pathway of Toxoplasma gondii.
BACKGROUND
Isoprenoids are an extensive group of natural products with diverse structures consisting of various numbers of five carbon isopentenyl diphosphate (IPP) units.


OBJECTIVE
We review here what is known about the isoprenoid pathway in T. gondii.


METHODS
Recent primary literature is reviewed.


CONCLUSIONS
Genomic evidence points toward the presence of a 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway, similar to the one found in plants, which will produce isopentenyl diphosphate (IPP). The DOXP/MEP pathway has been validated as a target in the related Apicomplexan parasite Plasmodium. The DOXP/MEP pathway in Toxoplasma has not been characterized. Downstream in the pathway, the enzyme farnesyl diphosphate synthase (FPPS) has a central role in forming important intermediates since farnesyl diphosphate (FPP) is a precursor of critical molecules with fundamental biological function such as dolichols, heme a, cholesterol, farnesylated proteins and others. Strong evidence indicates that this enzyme is a valid target for drugs since bisphosphonates, which are specific FPPS inhibitors, inhibited parasite growth in vitro and in vivo. Our hypothesis is that the isoprenoid pathway constitutes a major novel target for the treatment of toxoplasmosis.
Moreno
Silvia N J
SN
University of Georgia, Department of Cellular Biology and Center for Tropical and Emerging Global Diseases, 500 D. W. Brooks Dr, Athens, Georgia 30602, USA. smoreno@cb.uga.edu
Li
Zhu-Hong
ZH
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D013729:Terpenes / Q000008:administration & dosage* / Q000737:chemistry; D014122:Toxoplasma / Q000187:drug effects* / Q000502:physiology*; D014123:Toxoplasmosis / Q000188:drug therapy / Q000378:metabolism / Q000469:parasitology
D000890:Anti-Infective Agents; D013729:Terpenes