Phylogenetic Classification and Functional Review of Autotransporters

Abstract

Autotransporters are the core component of a molecular nano-machine that delivers cargo proteins across the outer membrane of Gram-negative bacteria. Part of the type V secretion system, this large family of proteins play a central role in controlling bacterial interactions with their environment by promoting adhesion to surfaces, biofilm formation, host colonization and invasion as well as cytotoxicity and immunomodulation. As such, autotransporters are key facilitators of fitness and pathogenesis and enable co-operation or competition with other bacteria. Recent years have witnessed a dramatic increase in the number of autotransporter sequences reported and a steady rise in functional studies, which further link these proteins to multiple virulence phenotypes. In this review we provide an overview of our current knowledge on classical autotransporter proteins, the archetype of this protein superfamily. We also carry out a phylogenetic analysis of their functional domains and present a new classification system for this exquisitely diverse group of bacterial proteins. The sixteen phylogenetic divisions identified establish sensible relationships between well characterized autotransporters and inform structural and functional predictions of uncharacterized proteins, which may guide future research aimed at addressing multiple unanswered aspects in this group of therapeutically important bacterial factors.

Crystal structure of a subtilisin-like autotransporter passenger domain reveals insights into its cytotoxic function

“…1b ). This β-helix is a common scaffold found in the majority of AT structures determined to date 39 , 45 – 51 . DALI analysis 43 of solely the β-helical stalk of Ssp indicated that this domain shares low structural similarity to known structures with the closest match being the C-terminal fragment of the AT IcsA from Shigella flexneri (15% identity, PDB: 5KE1 , Z-score: 15.7) with an r.m.s.d.…”

Identification and characterization of an HtrA sheddase produced byCoxiella burnetii

“…Similarly, it is possible to imagine that in the bacterial population, certain bacteria could lyse and thus directly release the soluble HtrA into the extracellular environment. In gram-negative bacteria (including Shigella and pathogenic E. Coli), there is a growing family of serine proteases secreted to the external milieu by a secretion mechanism called an autotransporter pathway (55,56). In the model of C. jejuni it was demonstrated that HtrA is expressed in the periplasmic space, but it can also be secreted into the extracellular environment and cleave the E-cad adherens junctions (57)(58)(59).…”

Genome-Wide Analysis of Antigen 43 (Ag43) Variants: New Insights in Their Diversity, Distribution and Prevalence in Bacteria

“…As an effector, the AT passenger domain can have a range of different functions, which have been used to classify ATs into distinct functional categories. One such category is the bacterial surface bound self-associating ATs (SAATs) [ 4 , 6 , 7 ], whose primary function is to interact and associate with SAATs on neighbouring bacterial surfaces. As a result of this homotypic interaction, bacterial cells aggregate together and sediment [ 7 , 8 ].…”

“…Prototypical members of SAATs include AIDA (adhesin involved in diffuse adherence), TibA (toxigenic invasion locus b), and Ag43 (antigen 43) [ 6 , 7 ]. The SAATs belong to the family of AIDA-type AT and, like many other AT adhesins, the passenger is predicted to be composed of right-handed β-helix structures (also called Type 1 AT passenger structure) [ 4 , 6 ].…”

“…Prototypical members of SAATs include AIDA (adhesin involved in diffuse adherence), TibA (toxigenic invasion locus b), and Ag43 (antigen 43) [ 6 , 7 ]. The SAATs belong to the family of AIDA-type AT and, like many other AT adhesins, the passenger is predicted to be composed of right-handed β-helix structures (also called Type 1 AT passenger structure) [ 4 , 6 ]. However, the SAATS are distinct from other adhesins, such as UpaB (uropathogenic E. coli autotransporter adhesin B) or EhaB (enterohemorrhagic Escherichia coli autotransporter B), which do not trigger autoaggregation but specifically bind some extracellular matrix molecules [ 6 , 10 ].…”