Abstract
Isoprenoid biosynthesis is essential for cell survival. Over 35 000 isoprenoid molecules have been identified to date in the three domains of life (bacteria, archaea and eukaryotes), and these molecules are involved in a wide variety of vital biological functions. Isoprenoids may be synthesized via one of two independent nonhomologous pathways, the classical mevalonate pathway or the alternative 2C-methyl-D-erythritol 4-phosphate (MEP) pathway. Given that isoprenoids are indispensable, enzymes involved in their production have been investigated as potential drug targets. It has also been observed that the MEP pathway intermediate 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMB-PP) can activate human Vγ9/Vδ2 T cells. Herein we review isoprenoid biosynthesis in bacterial pathogens. The role of isoprenoid biosynthesis pathways in host-pathogen interactions (virulence potential and immune stimulation) is examined. Finally, the design of antimicrobial drugs that target isoprenoid biosynthesis pathways is discussed.
Highlights
Isoprenoids are a large, diverse class of naturally occurring organic chemicals which are essential for cell survival
Analysis of the sequenced genomes suggests that synthesis of isopentyl diphosphate (IPP) in this human intestinal pathogen is via the methyl-D-erythritol 4-phosphate (MEP) pathway; the gene for the mevalonate pathway enzyme HMG-CoA reductase (HMGR) is present in all four sequenced Vibrio species (V. cholerae, Vibrio vulnificus, Vibrio parahaemolyticus and Vibrio fischeri)
The MEP pathway is the principal means of IPP biosynthesis in the majority of human pathogens
Summary
Isoprenoid biosynthesis is essential for cell survival. Over 35 000 isoprenoid molecules have been identified to date in the three domains of life (bacteria, archaea and eukaryotes), and these molecules are involved in a wide variety of vital biological functions. Isoprenoids may be synthesized via one of two independent nonhomologous pathways, the classical mevalonate pathway or the alternative 2C-methyl-D-erythritol 4-phosphate (MEP) pathway. Given that isoprenoids are indispensable, enzymes involved in their production have been investigated as potential drug targets. It has been observed that the MEP pathway intermediate 1-hydroxy-2methyl-2-(E)-butenyl 4-diphosphate (HMB-PP) can activate human Vc9/Vd2 T cells. We review isoprenoid biosynthesis in bacterial pathogens. The role of isoprenoid biosynthesis pathways in host–pathogen interactions (virulence potential and immune stimulation) is examined. The design of antimicrobial drugs that target isoprenoid biosynthesis pathways is discussed
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