The impact of orphan histidine kinases and phosphotransfer proteins on the regulation of clostridial sporulation initiation

Abstract

Sporulation is an important feature of the clostridial life cycle, facilitating survival of these bacteria in harsh environments, contributing to disease transmission for pathogenic species, and sharing common early steps that are also involved in regulating industrially important solvent production by some non-pathogenic species. Initial genomics studies suggested that Clostridia lack the classical phosphorelay that phosphorylates Spo0A and initiates sporulation in Bacillus , leading to the hypothesis that sporulation in Clostridia universally begins when Spo0A is phosphorylated by orphan histidine kinases (OHKs). However, components of the classical Bacillus phosphorelay were recently identified in some Clostridia. Similar Bacillus phosphorelay components have not yet been found in the pathogenic Clostridia or the solventogenic Clostridia of industrial importance. For some of those Clostridia lacking a classical phosphorelay, the involvement of OHKs in sporulation initiation has received support from genetic studies demonstrating the involvement of several apparent OHKs in their sporulation. In addition, several clostridial OHKs directly phosphorylate Spo0A in vitro . Interestingly, there is considerable protein domain diversity among the sporulation-associated OHKs in Clostridia. Further adding to the emergent complexity of sporulation initiation in Clostridia, several candidate OHK phosphotransfer proteins that were OHK candidates were shown to function as phosphatases that reduce sporulation in some Clostridia. The mounting evidence indicates that no single pathway explains sporulation initiation in all Clostridia and supports the need for further study to fully understand the unexpected and biologically fascinating mechanistic diversity of this important process among these medically and industrially important bacteria.

KipOTIA detoxifies 5-oxoproline and promotes the growth ofClostridioides difficile

“…We found that KipI and KipA do not have major effects on C. difficile sporulation, in contrast to B. subtilis , in which KipI impedes sporulation (Wang et al, 1997). The absence of a sporulation effect by the C. difficile Kip proteins is not completely surprising given the considerable differences in the genetic pathways and factors involved in sporulation initiation between B. subtilis and C. difficile (Edwards et al, 2022; Lee et al, 2022; Mehdizadeh Gohari et al, 2024). In B. subtilis, KipI binds to the sporulation activating kinase, KinA to repress spore formation (Jacques et al, 2011, 2008).…”

“…C. difficile infections are easily spread and difficult to contain because the spore form of the bacterium is resistant to disinfectants and allows the pathogen to survive nearly indefinitely in a dormant state (Ali et al, 2011;Shen, 2020). Although the structure and general form of C. difficile endospores are similar to other species, the environmental and nutritional conditions that lead to sporulation vary greatly among spore-forming bacteria (Lee et al, 2022;Mehdizadeh Gohari et al, 2024;Shen et al, 2019). While some basic nutritional requirements and regulatory factors are shared among the sporulating Firmicutes, it is not possible to predict the role of a given factor based on the presence of orthologs with a known function in another spore-former (A. N. Edwards et al, 2022Edwards et al, , 2014.…”

Molecular Markers and Regulatory Networks in Solventogenic Clostridium Species: Metabolic Engineering Conundrum

“…The σ B protein has been detected in C. acetobutylicum, and is known to modulate the stress response machinery (e.g., GrpE, DnaK DnaJ) in the microorganisms [96,98]. Additionally, the vegetative sigma factor (σ A ) in Clostridium species regulates the initiation of sporulation during the stationary phase (see [99] for a review on Clostridia sporulation). The sporulation-specific σ E and SpoIIGA genes required for the initiation of sporulation contain the σ A promoter-specific sequence along with 0A boxes consistent with the regulation of transcriptional activation by both σ A and Spo0A [100].…”