Clostridioides difficile Biology: Sporulation, Germination, and Corresponding Therapies for C. difficile Infection

@article{Zhu2018ClostridioidesDB,
  title={Clostridioides difficile Biology: Sporulation, Germination, and Corresponding Therapies for C. difficile Infection},
  author={Duolong Zhu and Joseph A. Sorg and Xingmin Sun},
  journal={Frontiers in Cellular and Infection Microbiology},
  year={2018},
  volume={8}
}
Clostridioides difficile is a Gram-positive, spore-forming, toxin-producing anaerobe, and an important nosocomial pathogen. Due to the strictly anaerobic nature of the vegetative form, spores are the main morphotype of infection and transmission of the disease. Spore formation and their subsequent germination play critical roles in C. difficile infection (CDI) progress. Under suitable conditions, C. difficile spores will germinate and outgrow to produce the pathogenic vegetative form. During… Expand
Updates to Clostridium difficile Spore Germination
TLDR
This review defines unique aspects of the germination pathways of C. difficile and compares them to those of two other well-studied organisms, Bacillus anthracis and Clostridium perfringens, and discusses the major discrepancies between current models of germination and areas of ongoing investigation. Expand
Loss of ClpP Function in Clostridioides difficile 630 Significantly Impacts Sporulation Systems
TLDR
The results demonstrate that ClpP, a promising target in other Gram-positive pathogens, holds promise as an anti-sporulation target in C. difficile. Expand
Terbium chloride influences Clostridium difficile spore germination.
TLDR
It is found that germination by spores prepared in peptone rich media, such as 70:30, is positively influenced by terbium, and it is hypothesized that, in these assays, Tb3+ functions similarly to calcium. Expand
Cwp22, a novel peptidoglycan cross-linking enzyme, plays pleiotropic roles in Clostridioides difficile.
TLDR
Cwp22 is involved in cell wall integrity and cell viability, which could affect most phenotypes of C. difficile R20291, and is an attractive target for CDI therapeutics and prophylactics, according to the Vaxign reverse vaccinology tool. Expand
A cortex-specific PBP contributes to cephalosporin resistance in Clostridium difficile
TLDR
This work has identified and characterised a penicillin binding protein (PBP) that is required for cortex synthesis in C. difficile and begins the process of unravelling cortex biogenesis in this important pathogen. Expand
Pharmacokinetics of CamSA, a Potential Prophylactic Compound against Clostridioides difficile Infections.
TLDR
It is hypothesized that the cycling of CamSA between the liver and intestines serves as a slow-release mechanism that allows CamSA to be retained in the gastrointestinal tract for days, explaining how a single CamSA dose can prevent murine CDI even though spores are present in the animal's intestine for up to four days post-challenge. Expand
CD25890, a conserved protein that modulates sporulation initiation in Clostridioides difficile
TLDR
The results suggest that CD25890 acts to modulate sporulation in response to the nutrients present in the environment. Expand
Temporal Variations in Patterns of Clostridioides difficile Strain Diversity and Antibiotic Resistance in Thailand
TLDR
Evidence of temporal changes in both C. difficile strains and patterns of antimicrobial resistance in Thailand is provided and metronidazole showed potent efficiency against most isolates in both groups. Expand
A cortex-specific penicillin-binding protein contributes to heat resistance in Clostridioides difficile spores
TLDR
This is the first characterisation of a cortex-specific PBP in C. difficile and begins the process of unravelling cortex biogenesis in this important pathogen. Expand
Anti-virulence strategies for Clostridioides difficile infection: advances and roadblocks
TLDR
The focus of this review is the conceptualization and development of specific anti-virulence strategies to combat CDI, and selects technologies that have advanced near, or beyond, pre-clinical testing, and discusses roadblocks associated with their development and implementation. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 104 REFERENCES
Clostridium difficile spore biology: sporulation, germination, and spore structural proteins.
TLDR
The regulation of the sporulation and germination pathways and the morphogenesis of the spore coat and exosporium will be discussed. Expand
Updates on Clostridium difficile spore biology.
TLDR
Recent advances on spore formation/germination in vitro and in-vivo, spore-host interactions, and spore resistance that contribute to the authors' knowledge of the role of C. difficile spores in the infectious process are summarized. Expand
Global Analysis of the Sporulation Pathway of Clostridium difficile
TLDR
These results provide the first genome-wide transcriptional analysis of genes induced by specific sporulation sigma factors in the Clostridia and highlight that diverse mechanisms regulate sporulations sigma factor activity in the Firmicutes. Expand
The Conserved Spore Coat Protein SpoVM Is Largely Dispensable in Clostridium difficile Spore Formation
TLDR
The requirement of the C. difficile homolog of SpoVM, a protein that is essential for spore formation in Bacillus subtilis due to its regulation of coat and cortex formation, is determined and it is shown that SpoVM is largely dispensable for C. diffusion, in contrast with B. subtILis. Expand
Bile Salts and Glycine as Cogerminants for Clostridium difficile Spores
TLDR
It is found that cholate derivatives and the amino acid glycine act as cogerminants and Deoxycholate, a metabolite of cholate produced by the normal intestinal flora, induced germination of C.difficile spores but prevented the growth of vegetative C. difficile. Expand
Germinants and Their Receptors in Clostridia
TLDR
This review focuses on the germinants and the receptors recognizing these germinant receptors in various clostridial species, which can help boost the production of chemicals, leading to cheaper ethanol-based fuels. Expand
Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores
TLDR
A signaling role for Ca2+ is described during C. difficile spore germination and direct evidence that intestinal Ca2- coordinates with bile salts to stimulate germination is provided, providing a biological mechanism that may explain why individuals with inefficient intestinal calcium absorption are more prone to CDI and suggest that modulating free intestinal calcium is a potential strategy to curb the incidence of CDI. Expand
Spores of Clostridium difficile Clinical Isolates Display a Diverse Germination Response to Bile Salts
TLDR
The data suggest that the mechanisms of C. difficile spore germination in response to bile salts are complex and require further study, and stresses the importance of studying multiple isolates in the future when analysing the nutrients or chemicals that either stimulate or inhibit C.difficile spores. Expand
Characterization of the Sporulation Initiation Pathway of Clostridium difficile and Its Role in Toxin Production
TLDR
Spo0A was directly phosphorylated by a putative sporulation-associated kinase, supporting the hypothesis that sporulation initiation in C. difficile is controlled by a two-component signal transduction system rather than a multicomponent phosphorelay. Expand
Conserved Oligopeptide Permeases Modulate Sporulation Initiation in Clostridium difficile
TLDR
The results indicate that the Opp and App transporters serve a different function in controlling sporulation and virulence in C. difficile than in Bacillus subtilis and suggest that nutrient availability plays a significant role in pathogenesis and sporulation in vivo. Expand
...
1
2
3
4
5
...