The stringent response in Myxococcus xanthus is regulated by SocE and the CsgA C-signaling protein

Myxococcus xanthus fruiting body development is induced by amino acid limit ation. The decision to grow or develop is established by the RelA-dependent stringent response and A-signaling. We identified two new members of this regulatory hierarchy, socE and the C-signaling gene csgA. SocE depletion ar rests growth and induces sporulation under conditions that normally favor g rowth as well as curtailing DNA and stable RNA synthesis, inhibiting cell e longation, and inducing accumulations of the stringent nucleotides ppGpp an d pppGpp [(p)ppGpp] This system separates C-signaling, which does not occur under these conditions, from CsgA enzyme activity. Amino acid substitution s in the CsgA eoenzyme binding pocket or catalytic site eliminate growth ar rest, relA mutation also eliminates growth arrest. Eleven pseudorevertants selected for growth following SocE depletion contained mutations in csgA or relA. These results suggest that CsgA induces the stringent response and w hile SocE inhibits it. Unlike the csgA mutant, wild-type and socE csgA cell s maintained high levels of (p)ppGpp throughout development. We suggest tha t CsgA maintains growth arrest throughout development to divert carbon from A-signaling and other sources into developmental macromolecular synthesis.