The intricate workings of a bacterial epigenetic switch

Advances in Experimental Medicine and Biology
Aaron D HerndayDavid Low

Abstract

Bacteria have developed epigenetic mechanisms to control the reversible Off-to-On switching of cell surface structures such as pyelonephritis-associated pili (PAP). The pap pili switch is primarily controlled by the global regulator leucine-responsive regulatory protein (Lrp), the local regulator PapI, and DNA adenine methylase (Dam). There are two sets of binding sites for Lrp in the pap regulatory region: promoter proximal sites 1,2,3 and promoter distal sites 4,5,6. The pilin promoter proximal (GATCprox) and distal (GATCdist) targets for Dam are located within Lrp binding sites 2 and 5, respectively. In the Off state, Lrp binds cooperatively to sites 1,2,3 overlapping the papBA pilin promoter, shutting off pilin transcription, and blocking methylation of GATCprox. Binding of Lrp at sites 1,2,3, together with methylation of GATCdist, reduces the affinity of Lrp for sites 4,5,6, preventing simultaneous binding of Lrp at sites 4,5,6 upstream. Switching to the phase. On state requires the environmentally regulated PapI co-regulator, which increases the affinity of Lrp for sites 5 and 2. PapI binds specifically to Lrp-pap DNA complexes via binding with Lrp as well as contact with DNA sequences within pap sites 5 and 2. Directiona...Continue Reading

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