The Response Regulator and Cyclic-Di-GMP Binding CbrR Is a Novel Regulator of Flagellar Motility.

A leading cause of bacterial gastroenteritis, is also associated with broad sequelae, including extragastrointestinal conditions such as reactive arthritis and Guillain-Barré Syndrome (GBS). CbrR is a response regulator that is annotated as a diguanylate cyclase (DGC), an enzyme that catalyzes the synthesis of c-di-GMP, a universal bacterial second messenger, from GTP. In DRH212, we constructed an unmarked deletion mutant, , and complemented mutant, . Motility assays indicated a hyper-motile phenotype associated with , whereas motility was deficient in . The overexpression of CbrR in was accompanied by a reduction in expression of FlaA, the major flagellin. Biofilm assays and scanning electron microscopy demonstrated similarities between DRH212 and ; however, was unable to form significant biofilms. Transmission electron microscopy showed similar cell morphology between the three strains; however, cells lacked flagella. Differential radial capillary action of ligand assays (DRaCALA) showed that CbrR binds GTP and c-di-GMP. Liquid chromatography tandem mass spectrometry detected low levels of c-di-GMP in and in expressing CbrR. CbrR is therefore a negative regulator of FlaA expression and motility, a critical virulence factor in pathogenesis.