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PMID: 22812521 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Review

Targeting iron assimilation to develop new antibacterials.

Expert opinion on drug discovery ·Vol. 7 ·No. 9 ·2012-09-00 ·Pages 831-47

Foley TL, Simeonov A

Abstract

Since the first application of antibiotics to treat bacterial infections, the development and spread of resistance has been a persistent threat. An ever evolving pipeline of next-generation therapeutics is required for modern medicine to remain one step ahead of pathogens. This review describes recent efforts to develop drugs that interrupt the assimilation of iron by bacteria: a process that is vital to cellular homeostasis and is not currently targeted by antibiotics used in the clinic. This review also covers the mechanisms by which bacteria acquire iron for their environment, and details efforts to intervene in these processes, using small molecule inhibitors that target key steps in these pathways, with a special emphasis on recent advances published during the 2010 - 2012 period. For decades, the routes used by bacteria to assimilate iron from host and environmental settings have been the subject of intense study. While numerous investigations have identified inhibitors of these pathways, many have stopped short of translating the in vitro results to in vivo proof of concept experiments. The extension of preliminary findings in this manner will significantly increase the impact of the field.

MeSH Terms
Anti-Bacterial Agents/therapeutic use Bacteria/metabolism Bacterial Infections/drug therapy,metabolism Chelation Therapy/methods Drug Discovery/methods Humans Iron/metabolism Siderophores/metabolism
Chemicals
Anti-Bacterial Agents Siderophores Iron
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Foley Timothy L
National Institutes of Health, National Center for Advancing Translational Sciences, Division of Preclinical Innovation, 9800 Medical Center Drive, Bethesda, MD 20892-3370, USA.
Simeonov Anton
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Article Info
Journal
Expert opinion on drug discovery
Abbr.
Expert Opin Drug Discov
ISSN
1746-045X
DOI
10.1517/17460441.2012.708335
Published
2012-09-00
Epub
2012-00-19
Pages
831-47
Language
English
Region
England
NLM ID
101295755
PMCID
PMC3434712
Subset
IM
Grants
Intramural NIH HHS · ZIB HG200319-08 · United States
External Links
PubMed source DOI: 10.1517/17460441.2012.708335 PMC Full Text View journal details
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