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

Extracytoplasmic function (ECF) σ factors are critical players in signal transduction networks involved in bacterial response to environmental changes. The Myxococcus 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 PQRS on illumination. This requires the CarD/CarG complex, the integration host factor (IHF) and a specific CarD‐binding site upstream of PQRS. 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.