Institut de Biologie StructuraleGrenoble / France

Contact person(s) related to this article / CONTRERAS-MARTEL Carlos

Virulence factors

Do bacteria have an immune system?

Wong, S.G. and Dessen, A. (2014) Structure of a bacterial alpha-2-macroglobulin reveals mimicry of eukaryotic innate immunity. Nature Comm. 5, 4917

Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. Surprisingly, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. Bacterial A2Ms are located in the periplasm where they are believed to provide protection to the cell by trapping external proteases through a covalent interaction with an activated thioester. This work reports the crystal structures and characterization of Salmonella enterica ser. Typhimurium A2M (Sa-A2M) in different states of thioester activation. The structures reveal thirteen domains whose arrangement displays high similarity to proteins involved in eukaryotic immune defense. A structural lock mechanism maintains the stability of the buried thioester, a requirement for its protease trapping activity. These findings indicate that bacteria have developed a rudimentary innate immune system whose mechanism mimics that of eukaryotes.