The CarD / CarG regulatory complex is required for the action of several members of the large set of M yxococcus xanthus extracytoplasmic function σ factors

Summary Extracytoplasmic function ( ECF ) σ factors are critical players in signal transduction networks involved in bacterial response to environmental changes. The M yxococcus xanthus genome reveals ∼45 putative ECF ‐σ factors, but for the overwhelming majority, the specific signals or mechanisms for selective activation and regulation remain unknown. One well‐studied ECF ‐σ, CarQ , binds to its anti‐σ, CarR , and is inactive in the dark but drives its own expression from promoter P QRS on illumination. This requires the CarD / CarG complex, the integration host factor ( IHF ) and a specific CarD ‐binding site upstream of P QRS . Here, we show that DdvS , a previously uncharacterized ECF ‐σ, activates its own expression in a CarD / CarG ‐dependent manner but is inhibited when specifically bound to the N ‐terminal zinc‐binding anti‐σ domain of its cognate anti‐σ, DdvA . Interestingly, we find that the autoregulatory action of 11 other ECF ‐σ factors studied here depends totally or partially on CarD / CarG but not IHF . In silico analysis revealed possible CarD ‐binding sites that may be involved in direct regulation by CarD / CarG of target promoter activity. CarD / CarG ‐linked ECF ‐σ regulation likely recurs in other myxobacteria with CarD / CarG orthologous pairs and could underlie, at least in part, the global regulatory effect of the complex on M . xanthus gene expression.