σ N ‐dependent control of acid resistance and the locus of enterocyte effacement in enterohemorrhagic E scherichia coli is activated by acetyl phosphate in a manner requiring flagellar regulator FlhDC and the σ S antagonist FliZ

In enterohemorrhagic Escherichia coli ( EHEC ), sigma factor N ( σ N ) regulates glutamate‐dependent acid resistance ( GDAR ) and the locus of enterocyte effacement ( LEE ); discrete genetic systems that are required for transmission and virulence of this intestinal pathogen. Regulation of these systems requires nitrogen regulatory protein C, NtrC, and is a consequence of NtrC‐ σ N ‐dependent reduction in the activity of sigma factor S ( σ S ). This study elucidates pathway components and stimuli for σ N ‐directed regulation of GDAR and the LEE in EHEC . Deletion of fliZ , the product of which reduces σ S activity, phenocopied rpoN ( σ N ) and ntrC null strains for GDAR and LEE control, acid resistance, and adherence. Upregulation of fliZ by NtrC‐ σ N was shown to be indirect and required an intact flagellar regulator flh DC . Activation of flh DC by NtrC‐ σ N and Flh DC ‐dependent regulation of GDAR and the LEE was dependent on σ N ‐promoter flh D P 2 , and a newly described NtrC upstream activator sequence. Addition of ammonium chloride significantly altered expression of GDAR and LEE , acid resistance, and adherence, independently of rpoN , ntrC , and the NtrC sensor kinase, ntrB . Altering the availability of NtrC phosphodonor acetyl phosphate by growth without glucose, with acetate addition, or by deletion of acetate kinase ackA , abrogated NtrC‐ σ N ‐dependent control of flh DC , fliZ , GDAR , and the LEE .