Bacteria can switch from a single-cell (planktonic) mode to a multicellular community (biofilm) mode via production of cell-cell aggregation and surface adhesion factors. In this report, we present evidence that the CsgD protein, a transcription regulator involved in biofilm formation in Escherichia coli, modulates the expression of the rpoS ( S ) regulon. Protein pattern analysis of E. coli cells in stationary phase shows that CsgD affects the expression of several proteins encoded by S -dependent genes. CsgD regulation of Sdependent genes takes place at gene transcription level, does not bypass the need for rpoS, and is abolished in an rpoS-null mutant. Consistent with these results, we find that CsgD expression leads to an increase in S intracellular concentration. Increase in S cellular amount is mediated by CsgD-dependent transcription activation of iraP, encoding a factor involved in S protein stabilization. Our results strongly suggest that the CsgD regulatory protein plays a major role as a relay between adhesion factors production and S -dependent gene expression via S protein stabilization. Direct coordination between biofilm formation and expression of the rpoS regulon could positively impact important biological processes, such as host colonization or response to environmental stresses.