Contribution of Trimeric Autotransporter C-Terminal Domains of Oligomeric Coiled-Coil Adhesin (Oca) Family Members YadA, UspA1, EibA, and Hia to Translocation of the YadA Passenger Domain and Virulence ofYersinia enterocolitica

Abstract

The Oca family is a novel class of autotransporter-adhesins with highest structural similarity in their C-terminal transmembrane region, which supposedly builds a beta-barrel pore in the outer membrane (OM). The prototype of the Oca family is YadA, an adhesin of Yersinia enterocolitica and Yersinia pseudotuberculosis. Protein secretion in gram-negative bacteria is faced with the serious problem of traversing two different membrane-lipid bilayers. Therefore, several secretory pathways have evolved, which were classified into five different types (9,11,20,29,51). Recently, even two novel multicomponent secretion systems, type VI and type VII secretion, were introduced (1,31,40). While all other types engage a whole machinery of protein exporting helper proteins, the type V secretion mechanism is thought to be less complex, since all necessary information for transport through both membranes is contained in the secreted protein itself, which has also led to the term "autotransporter" protein (20). With over 700 identified proteins to date, the type V secretion family is the largest group, and many of its members are also confirmed virulence factors with effector functions such as adherence, invasion, proteolysis, cytotoxicity, serum resistance, and cell-to-cell spread (14,37). An N-terminal signal peptide is Sec dependently cleaved during passage through the inner membrane, while the process of translocation through the outer membrane (OM) is still unresolved. The C-terminal region forms a beta-barrel pore before or during integration into the OM and is essential for translocation of the N-terminal passenger domain across the OM (20). However, the detailed process of passenger domain translocation remains unclear (6). Different models have been proposed to approach this issue. According to the hairpin and the threading model, the beta-barrel primarily integrates into the OM, and the passenger domain slides through the pore starting with the C or N terminus (21,36,39). The multimeric model suggests that the passenger domain is translocated to the bacterial surface through a central channel built by a multimeric complex of beta-barrel pores (52), while the Omp85 model involves the OM protein Omp85/YaeT in the translocation process (54, 55).Previously, we could demonstrate that the Yersinia adhesin YadA of Yersinia enterocolitica and Yersinia pseudotuberculosis is the prototype of a novel class of oligomeric autotransporter adhesins (42), which we termed Oca (for oligomeric coiled-coil adhesins), which can be found in alpha-, beta-, and gammaproteobacteria. In addition to YadA, several other family members, such as Hia and Hsf of Haemophilus influenzae, UspA1 and UspA2 of Moraxella catarrhalis, Eib proteins of Escherichia coli, or NadA of Neisseria meningitidis, have been identified in the last few years (8,12,15,23,45,48). Conventional autotransporters are monomeric proteins and form their C-terminal translocator domain (TLD) with 12 transmem-

Molecular Aspects ofMoraxella catarrhalisPathogenesis

“…The group of trimeric autotransporters is a large protein family consisting of virulence factors of diverse pathogenic gram-negative bacteria, such as the YadA protein of Yersinia spp. and the Hia protein of H. influenzae (1,33). Trimeric autotransporters mediate their own insertion into the outer membrane.…”

Trimer Stability of YadA Is Critical for Virulence of Yersinia enterocolitica

“…Recent studies by Ackermann et al (1) have shown that only the factual membrane anchor domain of YadA is able to confer serum resistance and mouse virulence to Y. enterocolitica expressing chimeric fusion proteins of the N-terminal YadA passenger domain and the C-terminal membrane anchor domains of the TAAs UspA1 (Moraxella catarrhalis), EibA (Escherichia coli), and Hia (Haemophilus influenzae).…”

Neisseria meningitidis Adhesin NadA Targets β1 Integrins

“…Therefore we investigated the ability of full-length NadA produced on the surface of Y. enterocolitica to mediate interaction with immobilized collagen type I, fibronectin, and matrigel, respectively, using an ELISA technique (22). As expected NadA-positive yersiniae failed to bind any of the tested ECM proteins in contrast to YadA-positive yersiniae which are known to bind to different ECM proteins (11,23) (supplemental Fig.…”