Iron Acquisition by Intracellular Pathogens
Pathogens that survive within cells are faced with the challenge of obtaining iron from the highly restrictive conditions within the host cell. Intracellular pathogens such as Salmonella typhimurium, Coxiella burnetti, Legionella pneumophila,
Francisella tularensis, and Mycobacterium tuberculosis all demonstrate a diminution in their pathogenicity upon iron deprivation (Collins 2003; Chlosta et al. 2006; Paradkar et al. 2008; Pan etal. 2010). Such pathogens survive intracellularly by occupying specific niches within the host cell and by hijacking available host iron. This is achieved by one or more mechanisms that can include: use of siderophores; expression of surface ferric reductases; heme uptake; and trafficking of transferrin (Schaible and Kaufmann 2004).
M. tb survives within the phagosome of macrophages, cells that are central to iron homeostasis. Numerous studies have demonstrated that M. tb has a very high requirement for iron, and iron overload (in the host) can cause a relapse of the disease (Trousseau 1872). An abundance of iron due to high dietary iron or iron supplementation has been shown to exacerbate the disease in both mouse models (Schaible et al. 2002) as well as human patients (Boelaert et al. 2007; Shemisa et al. 2014). In studies conducted on African patients, high dietary serum iron levels were found to be associated with greater mortality and morbidity due to tuberculosis (Gangaidzo et al. 2001; Isanaka et al. 2012).