The Escherichia coli MarA protein regulates the ycgZ‐ymgABC operon to inhibit biofilm formation

Summary The Escherichia coli marRAB operon is a paradigm for chromosomally encoded antibiotic resistance. The operon exerts its effect via an encoded transcription factor called MarA that modulates efflux pump and porin expression. In this work, we show that MarA is also a regulator of biofilm formation. Control is mediated by binding of MarA to the intergenic region upstream of the ycgZ‐ymgABC operon. The operon, known to influence the formation of curli fibres and colanic acid, is usually expressed during periods of starvation. Hence, the ycgZ‐ymgABC promoter is recognised by σ38 (RpoS)‐associated RNA polymerase (RNAP). Surprisingly, MarA does not influence σ38‐dependent transcription. Instead, MarA drives transcription by the housekeeping σ70‐associated RNAP. The effects of MarA on ycgZ‐ymgABC expression are coupled with biofilm formation by the rcsCDB phosphorelay system, with YcgZ, YmgA and YmgB forming a complex that directly interacts with the histidine kinase domain of RcsC. Expression of the multiple antibiotic resistance activator (MarA) protein can give rise to clinically relevant drug resistance in Escherichia coli. Counterintuitively, we showed that MarA production inhibits the formation of biofilms. Inhibition is mediated by the activation of the ycgZ‐ymgABC operon. To activate these genes, MarA acts selectively thus enhancing transcription by RNAP associated with the σ70 but not with the σ38 factor.