A non-canonical redox family protein regulates bacterial interaction machineries

Flagella and nanotubes are two major bacterial apparatuses involved in driving bacterial interactions. Flagella enable cells to perform exploratory roles, whereas nanotubes physically connect nearby cells, facilitating direct transfer of cytoplasmic materials. The only known regulatory protein in Bacillus subtilis that modulates nanotube biogenesis is metallophosphodiesterase YmdB, a global effector, through a route largely elusive. We report that YmdB recruits YdzF for nanotube production. YdzF is a MarR/DUF24 family transcriptional regulator belonging to MarR superfamily required for oxidative stress adaptation, a phenomenon executed by redox-sensing cysteine switches. However, YdzF behaves non-canonically due to proximally positioned intermolecular cysteine residues, hindering its conformational rearrangement. Independent of redox sensing, YdzF recognizes an unrelated flagellar Pfla/che promoter to modulate fla/che operon expression required for nanotube and flagella biogenesis. This promoter recognition by YdzF is entirely governed by YmdB. Furthermore, YdzF-mediated nanotube formation is widespread in Gram-positive bacteria.