9.B.50 The Outer Membrane Beta-barrel Endoprotease, Omptin (Omptin) Family
The Omptin family is a large family of outer membrane proteases/adhesins, found and studied primarily in enterobacteria (Kukkonen and Korhonen, 2004. They play important roles in the degradation of denatured periplasmic proteins (in E. coli), and funtion in pathogenesis (in Shigella, Escherichia, Yersinia and Salmonella species). In Yersinia pestis, the Pla protein is a plasminogen activator. It both activates plasminogen and inactivates α2-antiplasmin (Suomalainen et al., 2007). It also degrades complement components. In E. coli, omptins, OmpT and OmpP, have been shown to cleave and inactivate cationic antimicrobial peptides (Kukkonen and Korhonen, 2004), and peptide conformation is a specificity determinant (Brannon et al. 2015). OmpT of E. coli cleaves peptide bonds between two basic amino acids using a histidyl residue and an aspartyl residue at the active site of the protease, and surprisingly, this enzyme is functional in high concentrations of urea (Stathopoulos, 1998; Hritonenko and Stathopoulos, 2007).
The omptins Pla (Yersinia) and PgtE (Salmonella) attack innate immunity by affecting the plasminogen/plasmin, complement, coagulation, fibrinolysis, and matrix metalloproteinase systems. They also function by enhancing bacterial adhesiveness and invasiveness (Haiko et al., 2009; Yun and Morrissey, 2009; Korhonen et al., 2013). Although the mechanistic details and functions of Pla and PgtE differ, the outcome is the same: enhanced spread and multiplication of Y. pestis and S. enterica in the host. Maximal activity requires association with lipopolysaccharide (Hritonenko and Stathopoulos, 2007). Aprotinin is an omptin protease inhibitor (Brannon et al. 2015).