Novel and emerging sources of Clostridioides difficile infection

Turner, Nicholas; Smith, Becky; Lewis, Sarah S.

doi:10.1371/journal.ppat.1008125

Cited by 19 publications

(21 citation statements)

References 31 publications

(43 reference statements)

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“…There is an acute medical need to control gastrointestinal infections caused by Clostridioides difficile (also known as Clostridium difficile ) 1 – 3 . In the developed world, C. difficile is one of the leading causes of hospital-acquired infections, often following antibiotic therapy 4 .…”

Section: Introductionmentioning

confidence: 99%

Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix

et al. 2021

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Clostridioides difficile infections are an urgent medical problem. The newly discovered C.difficileadenine methyltransferase A (CamA) is specified by all C. difficile genomes sequenced to date (>300), but is rare among other bacteria. CamA is an orphan methyltransferase, unassociated with a restriction endonuclease. CamA-mediated methylation at CAAAAA is required for normal sporulation, biofilm formation, and intestinal colonization by C. difficile. We characterized CamA kinetic parameters, and determined its structure bound to DNA containing the recognition sequence. CamA contains an N-terminal domain for catalyzing methyl transfer, and a C-terminal DNA recognition domain. Major and minor groove DNA contacts in the recognition site involve base-specific hydrogen bonds, van der Waals contacts and the Watson-Crick pairing of a rearranged A:T base pair. These provide sufficient sequence discrimination to ensure high specificity. Finally, the surprisingly weak binding of the methyl donor S-adenosyl-l-methionine (SAM) might provide avenues for inhibiting CamA activity using SAM analogs.

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Section: Introductionmentioning

confidence: 99%

Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix

et al. 2021

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“…There is evidence that the epidemiology of CDI in humans is changing, with increasing numbers of cases reported from patients residing within the community and attribution of the source of infections in most of these cases is unknown (7,46). This study, in agreement with other recent studies shows that ribotypes associated within human clinical disease can be carried asymptomatically with the canine gut.…”

Section: Discussionmentioning

confidence: 99%

“…The availability of reliable tests for active toxin which are suitable for use in a diagnostic laboratory setting is likely to limit clinical investigations into the significance of toxigenic isolates. Cytotoxicity assays are labour intensive and unlikely to be widely available.There is evidence that the epidemiology of CDI in humans is changing, with increasing numbers of cases reported from patients residing within the community and attribution of the source of infections in most of these cases is unknown(7,46). This study, in agreement with other recent studies shows that ribotypes associated within human clinical disease can be carried asymptomatically with the canine gut.…”

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confidence: 99%

The duration of antibiotic treatment is associated with carriage of toxigenic and atoxigenic strains ofClostridioides difficilein dogs

Albuquerque

Pagnossin

Landsgaard

et al. 2021

Preprint

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Clostridioides difficile is a leading cause of human antibiotic-associated diarrhoeal disease globally. Zoonotic reservoirs of infection are increasingly suspected to play a role in the emergence of this disease in the community and dogs are considered as one potential source. Here we use a canine case-control study at a referral veterinary hospital in Scotland to assess: i) the risk factors associated with carriage of C. difficile by dogs, ii) whether carriage of C. difficile is associated with clinical disease in dogs and iii) the similarity of strains isolated from dogs with local human clinical surveillance. The overall prevalence of C. difficile carriage in dogs was 18.7% (95% CI 14.8-23.2%, n=61/327) of which 36% (n=22/61) were toxigenic strains. We found risk factors related to prior antibiotic treatment were significantly associated with C. difficile carriage by dogs. However, the presence of toxigenic strains of C. difficile in a canine faecal sample was not associated with diarrhoeal disease in dogs. Active toxin was infrequently detected in canine faecal samples carrying toxigenic strains (2/11 samples). Both dogs in which active toxin was detected had no clinical evidence of gastrointestinal disease. Among the ten toxigenic ribotypes of C. difficile detected in dogs in this study, six of these (012, 014, 020, 026, 078, 106) were ribotypes commonly associated with human clinical disease in Scotland, while atoxigenic isolates largely belonged to 010 and 039 ribotypes. Whilst C. difficile does not appear commonly associated with diarrhoeal disease in dogs, antibiotic treatment increases carriage of this bacteria including toxigenic strains commonly found in human clinical disease.

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“…There is evidence that the epidemiology of CDI in humans is changing, with increasing numbers of cases reported from patients residing within the community and attribution of the source of infections in most of these cases is unknown [ 7 , 53 ]. This study, in agreement with other recent studies shows that ribotypes associated within human clinical disease can be carried asymptomatically with the canine gut.…”

Section: Discussionmentioning

confidence: 99%

The duration of antibiotic treatment is associated with carriage of toxigenic and non-toxigenic strains of Clostridioides difficile in dogs

et al. 2021

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Clostridioides difficile is a leading cause of human antibiotic-associated diarrhoeal disease globally. Zoonotic reservoirs of infection are increasingly suspected to play a role in the emergence of this disease in the community and dogs are considered as one potential source. Here we use a canine case-control study at a referral veterinary hospital in Scotland to assess: i) the risk factors associated with carriage of C. difficile by dogs, ii) whether carriage of C. difficile is associated with clinical disease in dogs and iii) the similarity of strains isolated from dogs with local human clinical surveillance. The overall prevalence of C. difficile carriage in dogs was 18.7% (95% CI 14.8–23.2%, n = 61/327) of which 34% (n = 21/61) were toxigenic strains. We found risk factors related to prior antibiotic treatment were significantly associated with C. difficile carriage by dogs. However, the presence of toxigenic strains of C. difficile in a canine faecal sample was not associated with diarrhoeal disease in dogs. Active toxin was infrequently detected in canine faecal samples carrying toxigenic strains (2/11 samples). Both dogs in which active toxin was detected had no clinical evidence of gastrointestinal disease. Among the ten toxigenic ribotypes of C. difficile detected in dogs in this study, six of these (012, 014, 020, 026, 078, 106) were ribotypes commonly associated with human clinical disease in Scotland, while nontoxigenic isolates largely belonged to 010 and 039 ribotypes. Whilst C. difficile does not appear commonly associated with diarrhoeal disease in dogs, antibiotic treatment increases carriage of this bacteria including toxigenic strains commonly found in human clinical disease.

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Novel and emerging sources of Clostridioides difficile infection

Cited by 19 publications

References 31 publications

Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix

Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix

The duration of antibiotic treatment is associated with carriage of toxigenic and atoxigenic strains ofClostridioides difficilein dogs

The duration of antibiotic treatment is associated with carriage of toxigenic and non-toxigenic strains of Clostridioides difficile in dogs

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