Beyond proteostasis: Roles of type I chaperonins in bacterial pathogenesis

Abstract

Nearly all bacterial species express two or more chaperonin genes. Recent data indicate that type I chaperonins may be key players in bacterial infections. This is partly due to the well-known contribution of chaperonins in cellular proteostasis, the latter being compromised during bacterial host infection. In addition to their protein-folding activity, it has been revealed that certain chaperonins also exhibit moonlighting functions that can contribute in different ways to bacterial pathogenicity. Examples range from inducing adhesion molecules in Chlamydophila pneumoniae to supporting intracellular survival in Mycobacterium tuberculosis and Leishmania donovani, to inducing cytokines in Helicobacter pylori to promoting antimicrobial resistance in Escherichia coli, amongst others. This article provides a thorough reviews of our current understanding of the different mechanisms involving type I chaperonins during bacteria-host interactions, and suggests new areas to be explored and the potential of finding new targets for fighting bacterial infections.

The unfoldase ClpC1 of Mycobacterium tuberculosis regulates the expression of a distinct subset of proteins having intrinsically disordered termini

“…Typically, the multisubunit protease complex consists of the proteolytic component and regulatory ATPases. The ATPases chiefly perform the maintenance function (5), whereas proteases act as final executioners in the life cycle of proteins (6). Known cases of such multicompartmentalized systems such as Clp (caseinolytic protease), Lon protease, or 20S proteasome reveal that the executory nature of proteases is managed by their fundamental architecture comprising of multisubunit chambered structure with a central pore, whereas associated ATPases such as ClpX, ClpA, ClpC1, or 19S proteasome, which are commonly known as unfoldases, recognize, unfold, and translocate the prospective substrate proteins into the proteolytic chamber (7).…”