Iron acquisition strategies in mycobacteria. Issue 2 (March 2015)

• Record Type: Journal Article
• Authors: Fang, Zhuo; Sampson, Samantha Leigh; Warren, Robin Mark; Gey van Pittius, Nicolaas Claudius; Newton-Foot, Mae
• Is Part Of: Tuberculosis. Volume 95:Issue 2(2015)
• Page Start: 123
• Page End: 130
• Publication Date: 2015-03
• Subjects: 616.995
• DOI: 10.1016/j.tube.2015.01.004
• Languages: English
• ISSNs: 1472-9792

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Summary</title> <sec> <p id="abspara0010">Iron is an essential element to most life forms including mycobacterial species. However, in the oxidative atmosphere iron exists as insoluble salts. Free and soluble iron ions are scarce in both the extracellular and intracellular environment which makes iron assimilation very challenging to mycobacteria. Tuberculosis, caused by the pathogen, <italic>Mycobacterium tuberculosis</italic>, is one of the most infectious and deadly diseases in the world. Extensive studies regarding iron acquisition strategies have been documented in mycobacteria, including work on the mycobacterial iron chelators (siderophores), the iron-responsive regulon, and iron transport and utilization pathways. Under low iron conditions, expression of the genes encoding iron importers, exporters and siderophore biosynthetic enzymes is up-regulated significantly increasing the ability of the bacteria to acquire limited host iron. Disabling these proteins impairs the growth of mycobacteria under low iron conditions both <italic>in vitro</italic> and <italic>in vivo</italic>, and that of pathogenic mycobacteria in animal models. Drugs targeting siderophore-mediated iron transport could offer promising therapeutic options. However, the discovery and characterization of an alternative iron acquisition mechanism, the heme transport and utilization pathway, questions the effectiveness of the siderophore-centered therapeutic strategy. Links have been found between these two distinct iron acquisition mechanisms, thus, targeting a few candidate proteins or mechanisms may influence both pathways, leading to effective elimination of the bacteria in the host.</p> </sec> </abstract>