Diverse mechanisms regulate sporulation sigma factor activity in the Firmicutes

• Conserved sporulation sigma factors are differentially regulated in the Firmicutes.
• The order in which sporulation sigma factors function is not conserved.
• The mechanisms controlling σK activation are particularly divergent.
• C. difficile sigma factor activation is not strictly tied to morphological changes.

Sporulation allows bacteria to survive adverse conditions and is essential to the lifecycle of some obligate anaerobes. In Bacillus subtilis, the sporulation-specific sigma factors, σF, σE, σG, and σK, activate compartment-specific transcriptional programs that drive sporulation through its morphological stages. The regulation of these sigma factors was predicted to be conserved across the Firmicutes, since the regulatory proteins controlling their activation are largely conserved. However, recent studies in (Pepto)Clostridium difficile, Clostridium acetobutylicum, Clostridium perfringens, and Clostridium botulinum have revealed striking differences in the order, activation, and function of sporulation sigma factors. These studies indicate that gene conservation does not necessarily predict gene function and that new mechanisms for controlling cell fate determination remain to be discovered in the anaerobic Clostridia.