title: Iron acquisition strategies in mycobacteria.
abstract: 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, Mycobacterium tuberculosis, 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 in vitro and in vivo, 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.
authors: DST/NRF Centre of Excellence in Biomedical Tuberculosis Research, US/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Francie van Zijl Drive, Tygerberg, 7505, South Africa. Electronic address: zf@sun.ac.za.
authors: Zhuo
authors: Z
authors: Fang
authors: DST/NRF Centre of Excellence in Biomedical Tuberculosis Research, US/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Francie van Zijl Drive, Tygerberg, 7505, South Africa. Electronic address: ssampson@sun.ac.za.
authors: Samantha Leigh
authors: SL
authors: Sampson
authors: DST/NRF Centre of Excellence in Biomedical Tuberculosis Research, US/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Francie van Zijl Drive, Tygerberg, 7505, South Africa. Electronic address: rw1@sun.ac.za.
authors: Robin Mark
authors: RM
authors: Warren
authors: DST/NRF Centre of Excellence in Biomedical Tuberculosis Research, US/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, Francie van Zijl Drive, Tygerberg, 7505, South Africa. Electronic address: ngvp@sun.ac.za.
authors: Nicolaas Claudius
authors: NC
authors: Gey van Pittius
authors: Division of Medical Microbiology, Department of Pathology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Francie van Zijl Drive, Tygerberg, 7505, South Africa. Electronic address: maen@sun.ac.za.
authors: Mae
authors: M
authors: Newton-Foot
mesh_terms: D001426:Bacterial Proteins / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006418:Heme / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D009161:Mycobacterium / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D055571:Secretory Pathway / Q000502:physiology; D017262:Siderophores / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D017262:Siderophores; D006418:Heme; D007501:Iron
keywords: ESX; Heme; Iron; Mycobacteria