Mapping direct and indirect MarA/SoxS/Rob/RamA regulons in Typhimurium reveals repression of and biofilm formation.

The closely related transcription factors MarA, SoxS, Rob and RamA control overlapping stress responses in many enteric bacteria. Furthermore, constitutive expression of such regulators is linked to clinical antibiotic resistance. In this work we have mapped the binding of MarA, SoxS, Rob and RamA across the Typhimurium genome. In parallel, we have monitored changes in transcription start site use resulting from expression of the regulators. Together, these data allow direct and indirect gene regulatory effects to be disentangled. Promoter architecture across the regulon can also be deduced. At a phylogenetic scale, around one third of regulatory targets are conserved in most organisms encoding MarA, SoxS, Rob or RamA. We focused our attention on the control of , which encodes a transcriptional activator responsible for stimulating production of curli fibres during biofilm formation. We show that expression of is particularly sensitive to SoxS that binds upstream to repress transcription. This differs to the situation in , where MarA regulates indirectly.