Isoprenoid metabolism as a therapeutic target in gram-negative pathogens

Andrew J Wiemer; Chia-Hung Christine Hsiao; David F Wiemer

doi:10.2174/156802610793176602

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Isoprenoid metabolism as a therapeutic target in gram-negative pathogens

Journal article

Peer reviewed

Isoprenoid metabolism as a therapeutic target in gram-negative pathogens

Andrew J Wiemer, Chia-Hung Christine Hsiao and David F Wiemer

Current topics in medicinal chemistry, Vol.10(18), pp.1858-1871

2010

DOI: 10.2174/156802610793176602

PMID: 20615187

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Abstract

Gram-negative Enterobacteria include a variety of human pathogens, perhaps most notably E. coli, Salmonella, Shigella, Yersinia, and Proteus. While there are treatment options for the diseases caused by these organisms, multi-drug resistance is often a problem and development of novel antibiotics has lagged over recent years. In humans, the isoprenoid biosynthetic pathway has become a subject of intense research for therapeutic modulation of human enzymes in diseases including hypercholesterolemia, osteoporosis, and cancer. In bacteria, isoprenoid metabolism is arguably just as important, giving rise to components that are essential for electron transport and cell wall biosynthesis. Blocking these biosynthetic processes, either with the antibiotic fosmidomycin or by gene knockout strategies, has demonstrated the necessity of isoprenoid biosynthesis for bacterial growth. In this review, current knowledge of the biochemical pathways involved in farnesyl diphosphate metabolism in Enterobacteria, efforts to develop inhibitors of the involved enzymes, and insights from inhibitors of human isoprenoid metabolism that may be relevant for future studies of antibiotics that target these key enzymes, are described.

Animals

Benzoquinones - chemistry

Benzoquinones - metabolism

Cell Wall - metabolism

Electron Transport - drug effects

Gram-Negative Bacterial Infections - drug therapy

Gram-Negative Bacterial Infections - metabolism

Humans

Terpenes - chemistry

Terpenes - metabolism

Details

Title: Subtitle: Isoprenoid metabolism as a therapeutic target in gram-negative pathogens
Creators: Andrew J Wiemer - Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison WI 53706, USA
Chia-Hung Christine Hsiao
David F Wiemer
Resource Type: Journal article
Publication Details: Current topics in medicinal chemistry, Vol.10(18), pp.1858-1871
DOI: 10.2174/156802610793176602
PMID: 20615187
ISSN: 1568-0266
eISSN: 1873-4294
Language: English
Date published: 2010
Academic Unit: Neuroscience and Pharmacology; Chemistry
Record Identifier: 9984216698602771

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