160-167 JMB13-10015.fm

Oligopeptidase B (OpdB, E.C. 3.4.21.83) is a proteolytic enzyme that belongs to the prolyl oligopeptidase family (POP) of serine proteases [10, 24]. Initially discovered in E. coli, this enzyme was found in several gram-negative bacteria, spirochetes, [6, 24], and protozoa [5, 14], but not in higher eukaryotes, with the exception of some plants [6]. Although the physiological role of OpdB has not yet been elucidated in bacteria, it has been recently recognized as an important virulence factor in trypanosome infections [17, 18]. In particular, in infective forms of Trypanosoma cruzi, OpdB generates a calcium signalling factor that interacts with a receptor at the mammalian cell surface, triggering the intracellular mobilization of Ca2+ [4], an essential step for the trypanosome invasion. Deletion of the opdB gene in T. cruzi resulted in trypanosomes that were attenuated for virulence in a mouse model of infection [5]. In Trypanosoma brucei and Trypanosoma congolense, OpdB contributes to the pathogenesis of the infection through the anomalous degradation of biologically active peptides in the bloodstream of infected hosts [31]. Consistent with this view, the administration of irreversible OpdB inhibitors to trypanosomeinfected mice significantly impaired disease progression [19]. These results point out an important role of OpdB in the pathogenesis of parasitic diseases, and its potential as a novel target for antimicrobial therapy prompted an analysis of OpdB homologs in bacteria. Little is known about oligopeptidase B function in bacteria and no physiological substrates have been identified [6]. It has been previously observed that the OpdB from E. coli and Salmonella Typhimurium have a trypsin-like substrate specificity, cleaving peptides after basic residues of arginine and lysine [15, 16], and its hydrolytic activity is restricted to peptides shorter than 30-40 residues [7]. In a previous work, OpdB was associated with resistance of E. coli cells to certain antimicrobial peptides (AMPs) [13]. These are an integral part of the innate immune system that Received: October 7, 2013 Revised: November 12, 2013 Accepted: November 13, 2013