title: Invited review: Breaking barriers--attack on innate immune defences by omptin surface proteases of enterobacterial pathogens.
abstract: The omptin family of Gram-negative bacterial transmembrane aspartic proteases comprises surface proteins with a highly conserved beta-barrel fold but differing biological functions. The omptins OmpT of Escherichia coli, PgtE of Salmonella enterica, and Pla of Yersinia pestis differ in their substrate specificity as well as in control of their expression. Their functional differences are in accordance with the differing pathogenesis of the infections caused by E. coli, Salmonella, and Y. pestis, which suggests that the omptins have adapted to the life-styles of their host species. The omptins Pla and PgtE attack on innate immunity by affecting the plasminogen/plasmin, complement, coagulation, fibrinolysis, and matrix metalloproteinase systems, by inactivating antimicrobial peptides, and by enhancing bacterial adhesiveness and invasiveness. Although the mechanistic details of the functions of Pla and PgtE differ, the outcome is the same: enhanced spread and multiplication of Y. pestis and S. enterica in the host. The omptin OmpT is basically a housekeeping protease but it also degrades cationic antimicrobial peptides and may enhance colonization of E. coli at uroepithelia. The catalytic residues in the omptin molecules are spatially conserved, and the differing polypeptide substrate specificities are dictated by minor sequence variations at regions surrounding the catalytic cleft. For enzymatic activity, omptins require association with lipopolysaccharide on the outer membrane. Modification of lipopolysaccharide by in vivo conditions or by bacterial gene loss has an impact on omptin function. Creation of bacterial surface proteolysis is thus a coordinated function involving several surface structures.
authors.affiliation: General Microbiology, Faculty of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Haiko
authors.forename: Marjo
authors.initials: M
authors.lastname: Suomalainen
authors.forename: Teija
authors.initials: T
authors.lastname: Ojala
authors.forename: Kaarina
authors.initials: K
authors.lastname: Lähteenmäki
authors.forename: Timo K
authors.initials: TK
authors.lastname: Korhonen