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Updated: Jun 22, 2026
Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
Proteomic and genomic characterization of highly infectious Clostridium difficile 630 spores
Trevor D Lawley1, Nicholas J Croucher, Lu Yu
1Microbial Pathogenesis Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom. tl2@sanger.ac.uk
Abstract:
Clostridium difficile, a major cause of antibiotic-associated diarrhea, produces highly resistant spores that contaminate hospital environments and facilitate efficient disease transmission. We purified C. difficile spores using a novel method and show that they exhibit significant resistance to harsh physical or chemical treatments and are also highly infectious, with <7 environmental spores per cm(2) reproducibly establishing a persistent infection in exposed mice. Mass spectrometric analysis identified approximately 336 spore-associated polypeptides, with a significant proportion linked to translation, sporulation/germination, and protein stabilization/degradation. In addition, proteins from several distinct metabolic pathways associated with energy production were identified. Comparison of the C. difficile spore proteome to those of other clostridial species defined 88 proteins as the clostridial spore "core" and 29 proteins as C. difficile spore specific, including proteins that could contribute to spore-host interactions. Thus, our results provide the first molecular definition of C. difficile spores, opening up new opportunities for the development of diagnostic and therapeutic approaches.
Insights
Clostridium difficile spores are highly resistant and infectious, causing hospital-acquired diarrhea. This study defines their molecular makeup, revealing potential targets for new diagnostics and therapies against C. difficile infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Proteomics
Background:
- Clostridium difficile is a leading cause of hospital-acquired infections, primarily antibiotic-associated diarrhea.
- The highly resistant spores of C. difficile contribute to environmental contamination and disease transmission.
- Understanding the molecular composition of C. difficile spores is crucial for developing effective control strategies.
Purpose of the Study:
- To purify Clostridium difficile spores using a novel method.
- To characterize the proteome of C. difficile spores.
- To identify spore-specific proteins and potential targets for therapeutic intervention.
Main Methods:
- Novel purification technique for Clostridium difficile spores.
- Assessment of spore resistance to physical and chemical treatments.
- Mass spectrometry-based proteomic analysis of purified spores.
- Comparative proteomic analysis with other clostridial species.
Main Results:
- Purified C. difficile spores demonstrated high resistance and infectivity.
- Mass spectrometry identified approximately 336 spore-associated proteins, involved in translation, sporulation, and metabolism.
- A core set of 88 clostridial spore proteins and 29 C. difficile-specific proteins were identified.
- Specific proteins potentially involved in spore-host interactions were highlighted.
Conclusions:
- This study provides the first molecular definition of Clostridium difficile spores.
- The identified spore proteome offers insights into spore resistance and infectivity mechanisms.
- The findings open avenues for developing novel diagnostics and therapeutics against C. difficile.
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