Differential homotypic and heterotypic interactions of antigen 43 (Ag43) variants in autotransporter-mediated bacterial autoaggregation

Valentin Ageorges (1) , Marion Schiavone (2) , Grégory Jubelin (1) , Nelly Caccia (1) , Philippe Ruiz (1) , Ingrid Chafsey (1) , Xavier Bailly (3) , Etienne Dague (4) , Sabine Leroy (1) , Jason Paxman (5) , Begoña Heras (5) , Frédérique Chaucheyras-Durand (1, 2) , Amanda E Rossiter , Ian Henderson (6) , Mickaël Desvaux (1)

1 MEDIS - Microbiologie Environnement Digestif Santé
2 Lallemand SAS
3 UMR EPIA - Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques
4 LAAS-ELIA - Équipe Ingénierie pour les sciences du vivant
5 La Trobe University [Melbourne]
6 Institute of Microbiology and Infection

Antigen 43 (Ag43) is a cell-surface exposed protein of Escherichia coli secreted by the Type V, subtype a, secretion system (T5aSS) and belonging to the family of self-associating autotransporters (SAATs). These modular proteins, comprising a cleavable N-terminal signal peptide, a surface-exposed central passenger and an outer membrane C-terminal translocator, self-recognise in a Velcro-like handshake mechanism. A phylogenetic network analysis focusing on the passenger revealed for the first time that they actually distribute into four distinct classes, namely C1, C2, C3 and C4. Structural alignment and modelling analyses demonstrated these classes arose from shuffling of two different subdomains within the Ag43 passengers. Functional analyses revealed that homotypic interactions occur for all Ag43 classes but significant differences in the sedimentation kinetics and aggregation state were present when Ag43 C3 was expressed. In contrast, heterotypic interaction occurred in a very limited number of cases. Single cell-force spectroscopy demonstrated the importance of specific as well as nonspecific interactions in mediating Ag43-Ag43 recognition. We propose that structural differences in the subdomains of the Ag43 classes account for different autoaggregation dynamics and propensities to co-interact.

Domaines: Sciences du Vivant [q-bio]

Valentin Ageorges, Marion Schiavone, Grégory Jubelin, Nelly Caccia, Philippe Ruiz, et al.. Differential homotypic and heterotypic interactions of antigen 43 (Ag43) variants in autotransporter-mediated bacterial autoaggregation. Scientific Reports, 2019, 9 (1), pp.11100. ⟨10.1038/s41598-019-47608-4⟩. ⟨hal-02335796⟩