Regulation of the E. coli csgD gene encoding the master regulator of biofilm formation: Interplay between multiple transcription factors

Under stressful conditions in nature, Escherichia coli forms biofilms for long-term survival. Curli fimbriae are an essential architecture for cell-cell contacts within biofilms. Structural components and assembly factors of curli are encoded by two divergently arranged operons, csgBA and csgDEFG, which are regulated by the csgD gene product. Thus, CsgD is a master regulator of bacterial biofilm formation. Reflecting the response of biofilm formation to various external factors and conditions, the csgD promoter is under the control of multiple transcription factors including CRP, CpxR, Crl, H-NS, IHF, MlrA, OmpR, RcsB and RstA. We have conducted a systematic analysis of the regulation mechanism of the csgD promoter by these multiple transcription factors. After the DNA binding assays in vitro of various combinations of these factors with various segments of the csgD promoter as DNA probes, we realized not only competition between positive and negative regulators but also cooperative interplay within both positive and negative factor groups. These findings raise a regulation model, in which the csgD promoter is controlled by the relative levels of functional molecules of these transcription factors.