This review will concentrate on the germination of spores of bacilli, primarily because of the large amount of detailed knowledge of the germination of spores of these species compared to that of spores of clostridia. Consequently, there has long been applied interest in spore germination, with researchers seeking to understand this process better in order to either prevent spore germination or accelerate it and then kill the newly sensitive germinated spores. Germination is thus both an essential part of disease pathogenesis or food spoilage and a major weak spot in these organisms' life cycle. Invariably, it is the germination of spores of these organisms that leads to disease or food spoilage, and yet, when spores germinate and lose their dormancy, they lose their extreme resistance properties and become relatively easy to kill. The germination of the dormant and highly resistant spores formed by members of the Firmicutes phylum, in particular bacilli and clostridia, has long been of significant research interest for four major reasons, as follows: (i) fascinating regulatory systems allow such spores to remain in their dormant, resistant state for years and yet return to active growth in minutes (ii) while spores of most Firmicutes do not cause disease, spores of some bacilli and clostridia cause food spoilage and food-borne disease, as well as human diseases like gas gangrene, tetanus, botulism, anthrax, and pseudomembranous colitis (iii) spores of Bacillus anthracis are a major bioterrorism threat and (iv) spores of Clostridium difficile are an emerging public health threat ( 1, – 3). (i) How do nutrient germinants penetrate through spores' outer layers to access GRs in the IM? (ii) What happens during the highly variable and often long lag period between the exposure of spores to nutrient germinants and the commitment of spores to germinate? (iii) What do GRs and GerD do, and how do these proteins interact? (iv) What is the structure of the SpoVA channel in spores' IM, and how is this channel gated? (v) What is the precise state of the spore IM, which has a number of novel properties even though its lipid composition is very similar to that of growing cells? (vi) How is CLE activity regulated such that these enzymes act only when germination has been initiated? (vii) And finally, how does the germination of spores of clostridia compare with that of spores of bacilli? While much has been learned about nutrient germination, major questions remain unanswered, including the following.

These proteins include the (i) germinant receptors (GRs) that respond to nutrient germinants, (ii) GerD protein, which is essential for GR-dependent germination, (iii) SpoVA proteins that form a channel in spores' IM through which the spore core's huge depot of dipicolinic acid is released during germination, and (iv) cortex-lytic enzymes (CLEs) that degrade the large peptidoglycan cortex layer, allowing the spore core to take up much water and swell, thus completing spore germination. This process requires a number of spore-specific proteins, most of which are in or associated with the inner spore membrane (IM). Spores of Bacillus species can remain in their dormant and resistant states for years, but exposure to agents such as specific nutrients can cause spores' return to life within minutes in the process of germination.

Spore formation in bacillus subtilis