Targeting iron assimilation to develop new antibacterials.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
National Institutes of Health, National Center for Advancing Translational Sciences, Division of Preclinical Innovation, 9800 Medical Center Drive, Bethesda, MD 20892-3370, USA.
Timothy L
TL
Foley
Anton
A
Simeonov
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001419:Bacteria / Q000378:metabolism*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D015913:Chelation Therapy / Q000379:methods; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D017262:Siderophores / Q000378:metabolism
D000900:Anti-Bacterial Agents; D017262:Siderophores; D007501:Iron