, 1988; Lemanceau selleck kinase inhibitor et al., 2009). TonB-dependent receptors represent an Achilles’ heel in the bacterial outer membrane that is exploited by antimicrobial agents seeking to damage or destroy the

cell. An example of such agents is the bacteriocins, a diverse class of protein/peptide antimicrobials produced by Gram-negative bacteria to maintain their ecological niche against closely related competitors (Braun et al., 2002). Depending on their site of action, bacteriocins must traverse at least the outer and often both membranes to reach their target. To cross the outer membrane, many bacteriocins possess a receptor-binding domain that binds with high affinity to a TonB-dependent receptor. This positions the protein on the cell surface, leading

to interactions with the periplasmic Tol or Ton complexes that many bacteriocins exploit to facilitate cell entry (Chavan & Riley, 2007; Kleanthous, 2010a,b). In the recently identified bacteriocins, pectocins M1 and M2, from Pectobacterium, the receptor-binding domain consists of a horizontally acquired plant-like ferredoxin protein. Strains of Pectobacterium, which are susceptible to these pectocins, are also able to utilize selleck compound ferredoxin as an iron source (Grinter et al., 2012), suggesting firstly that Pectobacterium possesses a system for iron acquisition from plant ferredoxin and secondly that these pectocins have evolved to directly parasitize this system for cell entry. This review focuses on how iron acquisition through TonB-linked receptors, provides an advantage to Gram-negative pathogens during pathogenesis and how bacteriocins, specifically

pectocins M1 and M2, have evolved to take advantage of these receptors for cell entry. The most common strategy applied by bacteria to acquire iron from their environment is the synthesis and excretion of iron-chelating siderophores. Siderophores are structurally diverse, with almost 500 identified to date and generally consist of a flexible, often peptide-derived scaffold with a number of functional groups for coordinating iron (Krewulak & Vogel, 2008). These SSR128129E functional groups (α-hydroxycarboxylic acid, catechol and hydroxamic acid) possess two oxygen atoms which coordinate ferric iron in a bidentate fashion (Boukhalfa & Crumbliss, 2002). This geometry allows siderophores to bind iron with an exceedingly high affinity at physiological pH. As such, siderophores play a pivotal role in pathogenesis of many bacteria including Pseudomonas aeruginosa and Yersinia sp. (Mossialos & Amoutzias, 2009; Fetherston et al., 2010). After the secreted siderophores have bound iron, they are sequestered by specific TonB-dependent outer membrane receptors and the iron–siderophore complex is imported into the periplasm (Braun & Hantke, 2011).