Self-perpetuating epigenetic pili switches in bacteria

Abstract

Cis-and Trans-Acting Pap Switch ComponentsB acteria have developed phase variation mechanisms to control cell surface pili-adhesin complexes between expression (phase ON) and nonexpression (phase OFF) states. Pili phase variation can occur by site specific (1, 2) and homologous recombination (3) mechanisms. In addition, a large group of pili operons including pyelonephritis-associated pili (pap) are regulated by an epigenetic switch directly controlled by DNA methylation pattern formation (4, 5). The focus of this paper is on the mechanisms by which the phase OFF and phase ON states are perpetuated, the transition between phase OFF and phase ON states, and the external inputs that control phase switching.

Regulation of bacterial virulence gene expression by cell envelope stress responses

“…A full description of this complicated mechanism is far beyond the scope of this review, but others have covered it extensively. 92,93 In brief, the global regulator Lrp (leucine-responsive regulatory protein) binds to distal activating or proximal repressing sites within the pap regulatory region. The Lrp binding location is influenced by the methylation state of GATC sequences, which is influenced by Dam methylase and the local regulatory proteins PapB and PapI.…”

“…The Lrp binding location is influenced by the methylation state of GATC sequences, which is influenced by Dam methylase and the local regulatory proteins PapB and PapI. 93 It is thought that phase switching requires DNA replication to dissociate Lrp-DNA complexes and to generate a hemimethylated GATC site. Regardless, CpxR competes with Lrp for binding to both promoter proximal and distal binding sites.…”

DNA methylation in Yersinia enterocolitica: role of the DNA adenine methyltransferase in mismatch repair and regulation of virulence factors

“…The expression of Pap pili is subject to phase variation, which occurs without a DNA sequence change. Instead, the methylation pattern of two GATC sites proximal to the papBA promoter influences the binding of the regulatory proteins Lrp and PapI, which correlates with the ON and the OFF stage of pilus expression (Hernday et al, 2002).…”

Unique organization and regulation of the mrx fimbrial operon in Xenorhabdus nematophila

“…The pap operon is regulated by a complex mechanism involving local regulatory proteins (PapB, PapI), the leucine-responsive regulatory protein (Lrp), cyclic AMP receptor protein (CRP), and the differential site-specific methylation of two GATC sites situated upstream of the promoter (Hernday et al, 2002). The fim operon of E. coli and the mrp operon of Proteus mirabilis are regulated by a recombinase-mediated inversion of a promoter-bearing invertible element.…”