Gene synteny and translational coupling of sctS and sctT facilitate assembly of the unique helical T3SS export apparatus in Salmonella Typhimurium

Résumé fourni par la source

Abstract Virulence-associated type III secretion systems (T3SS) are employed by many gram-negative pathogens to translocate effector proteins into hosts. These nanomachines are composed of cytoplasmic components, a needle complex base, housing the export apparatus and anchoring the machine in the bacterial cell envelope, a needle filament, and a translocon that penetrates the host membrane. Assembly of the T3SS is a hierarchical process, which is initiated by coordinated association of the five subunits comprising the export apparatus, SctR, SctS, SctT, SctU, and SctV, in the bacterial inner membrane. In this study, we report that proper assembly of this uniquely helical export apparatus is fine-tuned by the genetic organization of the export apparatus genes in Salmonella Typhimurium. The sctS mRNA harbors a stem-loop structure which conceals the Shine-Dalgarno sequence of sctT from recognition by a ribosome. sctT translation is only possible upon melting of the stem-loop by a sctS -translating ribosome. This mechanism translationally couples sctS and sctT. We show that this strict regulation prevents uncontrolled overexpression of SctT and its assembly into futile multimers that disrupt export apparatus assembly and reduce pathogen fitness. Based on the strong synteny of T3SS export apparatus genes and their highly conserved unique structure, also among closely related bacterial flagella, similar mechanisms are likely needed to enable a tightly regulated and stoichiometric assembly process of these molecular machines in general.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.