The engulfasome in C. difficile: Variations on protein machineries

Abstract

Clostridioides difficile infection (CDI) continues to be a substantial healthcare burden, and the changing disease profile raises new challenges in CDI management, both in clinical settings and in the community. CDI is transmitted by spores, which are formed by a subset of the cell population where an asymmetric septum is formed. A full copy of the chromosome is transported into the smaller compartment which is then engulfed by the mother cell. After engulfment, multiple metabolic and morphological changes occur, eventually resulting in the release of the mature spore. Whilst studies in the model organism Bacillus subtilis have demonstrated the importance of the DMP and Q:AH machineries in engulfment, it is becoming clear that there are fundamental differences in the way the two organisms organise these machineries. As spores are the infectious agent in CDI, it is crucial to understand how these dormant cells are formed, and how sporulation can be prevented or disrupted with the view of reducing CDI. Here, we review the current literature on the DMP and Q:AH machineries in C. difficile, and how they compare and contrast to those of B. subtilis.

Distribution and preservation of the components of the engulfment. What is beyond representative genomes?

“…The patchy distribution observed in the phyletic patterns across the 954 Firmicutes and the prediction of orthologs in previous works [ 7 – 9 , 29 , 65 ], show that the sporulation genes, even those defined as signatures, may be missing in some species. Several authors postulated that horizontal gene transfer and loss events may be important evolutionary forces of the sporulation genes among Firmicutes.…”

“…To perform the analysis, we employed a methodology of our own that can discover distant POs based on the construction of protein architectures using Pfam profiles that describe the proteins of the Q:AH and DMP complexes that form a structure recently named engulfasome [ 9 ] and the accessory proteins SpoIIB, which is suggested to regulate the septal thinning during engulfment in B . subtilis [ 33 ], and GerM that probably localizes SpoIIQ in the Q:AH complex also in B .…”

“…difficile whose experimental evidence shows differences in the regulation and mechanisms and in the genes needed to promote engulfment [ 1 , 18 , 19 ]. The differences were also found in other stages of sporulation that have been the object of study by groups that, given the lack of or little experimental evidence in other species, have been motivated to search for these differences by sequences comparison, and some of them have found genes that serve as sporulation markers or signatures [ 5 , 7 – 9 , 29 , 76 ]. However, the prevalence of sporulation markers among the “asporogenic” species of Firmicutes and the absence of some of them in sporulating species generate important questions regarding their evolution in the phylum.…”

“…However, the prevalence of sporulation markers among the “asporogenic” species of Firmicutes and the absence of some of them in sporulating species generate important questions regarding their evolution in the phylum. Particularly, in the cases of the genes involved in engulfment, several studies have identified the products of the spoIIIA operon as part of the core genes conserved in endospore formers [ 5 , 7 – 9 , 29 , 76 ]. Our findings that consider 954 Firmicutes show that the genes of the operon prevail in the highest proportion of endospore formers in contrast to the genes that do not form spores, which is a result shown in other reports.…”

“…An example of these are the studies performed by Ribis et al, who propose that the expression of spoIIP encoding SpoIIP, under the control of σ F in C . difficile and σ E in B subtilis , may not be necessarily anchored to the forespore membrane throughout engulfment [ 20 ], which signifies a different organization and action mechanisms of the DMP machinery between both species and is a trait also suggested by other works [ 9 , 15 , 20 , 21 ]. The engulfment in B .…”