The virulence regulator VirB from Shigella flexneri uses a CTP-dependent switch mechanism to activate gene expression

The virulence regulator VirB from Shigella flexneri uses a CTP-dependent switch mechanism to activate gene expression

Blog Article

Abstract The transcriptional antisilencer VirB acts as a master regulator of virulence gene expression in the human pathogen Shigella flexneri.It binds DNA sequences (virS) upstream of VirB-dependent promoters and counteracts their silencing by the nucleoid-organizing protein H-NS.However, its precise mode of action remains unclear.Notably, VirB is not a classical transcription factor but related to ParB-type DNA-partitioning proteins, which have recently been recognized as DNA-sliding clamps using CTP binding and hydrolysis Tracking to control their DNA entry gate.Here, we show that VirB binds CTP, embraces DNA in a clamp-like fashion upon its CTP-dependent loading at virS sites and slides laterally on DNA after clamp closure.

Mutations that prevent CTP-binding block VirB loading in vitro and abolish the formation of VirB nucleoprotein complexes as well as virulence Psoriasis gene expression in vivo.Thus, VirB represents a CTP-dependent molecular switch that uses a loading-and-sliding mechanism to control transcription during bacterial pathogenesis.