The Bacterial Intimins and Invasins: A Large and Novel Family of Secreted Proteins

Abstract

BackgroundGram-negative bacteria have developed a limited repertoire of solutions for secreting proteins from the cytoplasmic compartment to the exterior of the cell. Amongst the spectrum of secreted proteins are the intimins and invasins (the Int/Inv family; TC# 1.B.54) which are characterized by an N-terminal β-barrel domain and a C-terminal surface localized passenger domain. Despite the important role played by members of this family in diseases mediated by several species of the Enterobacteriaceae, there has been little appreciation for the distribution and diversity of these proteins amongst Gram-negative bacteria. Furthermore, there is little understanding of the molecular events governing secretion of these proteins to the extracellular milieu.Principal Findings In silico approaches were used to analyze the domain organization and diversity of members of this secretion family. Proteins belonging to this family are predominantly associated with organisms from the γ-proteobacteria. Whilst proteins from the Chlamydia, γ-, β- and ε-proteobacteria possess β-barrel domains and passenger domains of various sizes, Int/Inv proteins from the α-proteobacteria, cyanobacteria and chlorobi possess only the predicted β-barrel domains. Phylogenetic analyses revealed that with few exceptions these proteins cluster according to organismal type, indicating that divergence occurred contemporaneously with speciation, and that horizontal transfer was limited. Clustering patterns of the β-barrel domains correlate well with those of the full-length proteins although the passenger domains do so with much less consistency. The modular subdomain design of the passenger domains suggests that subdomain duplication and deletion have occurred with high frequency over evolutionary time. However, all repeated subdomains are found in tandem, suggesting that subdomain shuffling occurred rarely if at all. Topological predictions for the β-barrel domains are presented.ConclusionBased on our in silico analyses we present a model for the biogenesis of these proteins. This study is the first of its kind to describe this unusual family of bacterial adhesins.

Role of a New Intimin/Invasin-Like Protein in Yersinia pestis Virulence

“…This family, for which E. coli O157 intimin and Y. pseudotuberculosis invasin are archetypal, is now recognized in a number of Gramnegative organisms (31). The Ilp protein conforms to the general characteristics of this family, evidenced by an N-terminal signal sequence and N-terminal LysM domain, a highly conserved ␤-domain predicted to conform to a transmembrane ␤-barrel structure, and a C-terminal passenger domain localized on the cell surface.…”

“…The hmsHFRS and gmhS genes, encoding an extracellular polysaccharide and a modification of lipopolysaccharide core, respectively, are required for the formation of biofilm and blockage in the flea (7,13). Because several members of the intimin/invasin family of proteins have been implicated in biofilm formation (31) and because Ilp is expressed at lower temperatures, we investigated the potential role of Ilp on blockage and infectivity in the flea. Results showed that there were no differences in the blockage and infection rates by Y. pestis KIM6 ⌬ilp compared to those of the parental wild-type strain, suggesting that Ilp has a limited role, if any, in the transmission of Y. pestis from a flea to a mammalian host.…”

In Vivo -Induced InvA-Like Autotransporters Ifp and InvC of Yersinia pseudotuberculosis Promote Interactions with Intestinal Epithelial Cells and Contribute to Virulence

“…This domain can be found in peptidoglycan-degrading enzymes (autolysins) and is predicted to bind peptidoglycan (3,56). It might act as an additional base to stabilize the ␤-barrel autotransport structure of the large surfaceexposed portion of InvC (60). Alternatively, the LysM-type domain might be implicated in the translocation of the outer membrane protein through the cross-linked peptidoglycan layer (50).…”

“…This part of the protein is predicted to form a ␤-barrel structure in the outer membrane (OM), acting as an autotransporter of the surface-exposed C terminus. It is absolutely required for the secretion, assembly, and incorporation of the molecules into the OM and is necessary for the proper surface presentation of the cell adhesion domain (60). The cell binding activity of invasin and the intimins is localized within the last C-terminal amino acids.…”

Adhesines of the Plague Agent

“…к этой группе аутотран-спортных белков относят инвазин энтеропатогенных бактерий Y. pseudotuberculosis и Y. enterocolitica [46]. в клетках возбудителя чумы ген inv инактивирован вставкой IS200, но присутствует его гомолог [30].…”