The microcin undergoes post-translational modification with a trimer of N-(2,3-dihydroxybenzoyl) linked to the C-terminal serine residue by a β-d-glucose. This modification which has been shown to bind iron mimics a catechol-type siderophore and significantly increases the toxicity of the peptide (Thomas et al., 2004; Destoumieux-Garzón et al., 2006). A number of bacterial pathogens with specific mammalian hosts possess systems for

directly obtaining iron from host proteins such as transferrin and lactoferrin, which sequester free iron in the body’s extracellular fluids. The most thoroughly characterized of these systems is the transferrin transport system of Neisseria gonorrhoeae and Neisseria meningitidis (Noinaj et al., 2012). Transferrin-binding protein A (TbpA),

a 100 kDa integral outer membrane protein and transferrin-binding protein Galunisertib supplier B (TbpB) an 80 kDa membrane anchored coreceptor form the basis of this system. TbpA, a TonB-dependent receptor strongly binds transferrin and acts as the conduit for transport of the liberated ferric iron across the outer membrane; however, it lacks the ability to distinguish between the apo and holo forms of the protein (Moraes et al., 2009). The coreceptor TbpB has a strong affinity for the iron loaded transferrin Nivolumab order only and acts synergistically with TbpA, considerably increasing the efficiency of iron import (Anderson et al., 1994). Following binding and extraction of iron, apo-transferrin is released from the complex (Lee & Schryvers, 1988). The importance of

this system for fitness is demonstrated by the fact that its inactivation renders N. gonorrhoeae avirulent (Cornelissen et al., 1998). The majority of iron in a mammalian host is stored intracellularly as haemoglobin (Rohde et al., 2002). As such, haemoglobin Bcl-w and the haem it contains represent an important iron source for invading pathogens (Wandersman & Stojiljkovic, 2000). As a result, pathogenic bacteria commonly secrete haemolysins and cytolysins that lyse host cells and release haemoglobin and other haemoproteins (Krewulak & Vogel, 2008). Uptake of the liberated haem is then achieved by a number of specialized systems, which in Gram-negative bacteria generally consist of a TonB-dependent outer membrane receptor, a periplasmic-binding protein and an ABC transporter (Tong & Guo, 2009). An example of a system, where a cell surface receptor directly acquires free or protein-bound haem, is the two-component HpuA/B system of N. meningitidis, which is evolutionarily and mechanistically related to the transferrin-binding system discussed earlier (Rohde et al., 2002). A second system indentified in a number of Gram-negative bacteria and characterized in the opportunistic pathogens P.