A wide spectrum of bacterial species including E.coli, M. tuberculosis, P aeruginosa,
S. tymphimurium, Bordetella pertusis, Y. pestis, Vibrio cholera and S. aureus are known to synthesize a variety of high-affinity metal chelators that withdraw and acquire iron from host resources (Ratledge and Dover 2000). Siderophores possess an exceedingly high affinity for iron of the order 1030, which is significantly more than that of transferrin (1023); they therefore steal iron from host resources. Based on their chemical nature, siderophores are classified as phenolic ring-based structures where hydroxyl or dihydroxybenzoic acid chelates Fe3+, hydroxam- ates, or mixed ligands ofthe previous two categories (Ratledge 2004). Biosynthesis of these molecules is initiated in response to iron deficiency and is tightly regulated.
Transferrin Iron Acquisition
Transferrin is an abundantly present serum protein; it has a bi-lobed structure with a single Fe3+ ion binding to each lobe (Gomme et al. 2005). Several pathogenic organisms such as N. gonorrhoea, N. meningitidis, A. pleuropneumoniae and H. influenzae directly capture host transferrin or lactoferrin at their surface. The specific transferrin-binding proteins TbpA and TbpB and the equivalent lactoferrin-binding proteins LbpA and LbpB are responsible for cell-surface sequestration of host iron carrier proteins. Iron is then released from the mammalian host carrier protein and transported across the microbial membrane in a TonB-dependent manner (Gray-Owen and Schyvers 1996).
In the Gram-positive bacteria S. aureus and S. epidermidis, cell-surface GAPDH (along with other proteins) have been reported to function as receptors for transferrin (Modun and Williams 1999; Taylor and Heinrichs 2002). It has been suggested that the reductase activity of GAPDH causes the release and internalization of iron from surface-sequestered transferrin (Ratledge and Dover 2000). Lastly, a unique survival strategy is adopted by Borrelia burgdorferi (the causative agent of Lyme disease), where it completely circumvents the requirement of iron uptake. This organism has evolved to utilize manganese as a cofactor in metalloenzymes instead of iron (Posey and Gherardini 2000).