The Impact of Gene Silencing on Horizontal Gene Transfer and Bacterial Evolution

The H-NS family of DNA-binding proteins is the subject of intense study due to its important roles in the regulation of horizontally acquired genes critical for virulence, antibiotic resistance, and metabolism. Xenogeneic silencing proteins, typified by the H-NS protein of Escherichia coli, specifically target and downregulate expression from AT-rich genes by selectively recognizing specific structural features unique to the AT-rich minor groove. In doing so, these proteins facilitate bacterial evolution; enabling these cells to engage in horizontal gene transfer while buffering potential any detrimental fitness consequences that may result from it. Xenogeneic silencing and counter-silencing explain how bacterial cells can evolve effective gene regulatory strategies in the face of rampant gene gain and loss and it has extended our understanding of bacterial gene regulation beyond the classic operon model. Here we review the structures and mechanisms of xenogeneic silencers as well as their impact on bacterial evolution. Several H-NS-like proteins appear to play a role in facilitating gene transfer by other mechanisms including by regulating transposition, conjugation, and participating in the activation of virulence loci like the locus of enterocyte effacement pathogenicity island of pathogenic strains of E. coli. Evidence suggests that the critical determinants that dictate whether an H-NS-like protein will be a silencer or will perform a different function do not lie in the DNA-binding domain but, rather, in the domains that control oligomerization. This suggests that H-NS-like proteins are transcription factors that both recognize and alter the shape of DNA to exert specific effects that include but are not limited to gene silencing.