MdfA is a novel ClpC adaptor protein that functions in the developing <i>Bacillus subtilis</i> spore

Bacterial protein degradation machinery consists of chaperone-protease complexes that play vital roles in bacterial growth and development and have sparked interest as novel antimicrobial targets. ClpC-ClpP (ClpCP) is one such chaperone-protease complex, recruited by adaptors to specific functions in the model bacterium <i>Bacillus subtilis</i> and other Gram-positive bacteria, including the pathogens <i>Staphylococcus aureus</i> and <i>Mycobacterium tuberculosis</i> Here we have identified a new ClpCP adaptor protein, MdfA (metabolic differentiation factor A; formerly YjbA), in a genetic screen for factors that help drive <i>B. subtilis</i> toward metabolic dormancy during spore formation. A knockout of <i>mdfA</i> stimulates gene expression in the developing spore, while aberrant expression of <i>mdfA</i> during vegetative growth is toxic. MdfA binds directly to ClpC to induce its oligomerization and ATPase activity, and this interaction is required for the in vivo effects of <i>mdfA</i> Finally, a cocrystal structure reveals that MdfA binds to the ClpC N-terminal domain at a location analogous to that on the <i>M. tuberculosis</i> ClpC1 protein where bactericidal cyclic peptides bind. Altogether, our data and that of an accompanying study by Riley and colleagues support a model in which MdfA induces ClpCP-mediated degradation of metabolic enzymes in the developing spore, helping drive it toward metabolic dormancy.