The non-toxigenic strain of Clostridioides difficile Z31 can prevent infection by C. difficile in experimental model piglets

Júnior, Carlos Augusto de Oliveira; Silva, Rodrigo; Cruz, Diogo Soares Gonçalves; Pires, Isadora Honorato; Guedes, Roberto Maurício Carvalho; Lobato, Francisco Carlos Faria

doi:10.1016/j.anaerobe.2018.10.002

Cited by 9 publications

(7 citation statements)

References 28 publications

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“…The control group in this study also had a slightly higher prevalence of colonization by NTCD. These findings suggest that NTCD may prevent colonization by toxigenic C. difficile and the subsequent development of CDI, as reported previously (27,28); however, a larger study is needed to properly evaluate the effects of colonization by NTCD in humans.…”

Section: Discussionsupporting

confidence: 81%

“…To investigate one possible protective factor, the effect of colonization by NTCD on subsequent CDI severity was evaluated. In animal studies, colonization by NTCD can be protective against recurrence of CDI, most likely due to competition with toxigenic strains to colonize the colon (27,28). Although the number of colonized patients was low in this study (26 cases, 10%) and there was no significant difference, there was a trend toward less severe disease in CDI patients colonized by NTCD.…”

Section: Discussioncontrasting

confidence: 52%

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Mild or Malign: Clinical Characteristics and Outcomes of Clostridium difficile Infection in Thailand

et al. 2020

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Little is known about the clinical characteristics of Clostridium difficile infection (CDI) in Asia in general, and Thailand specifically, with a few studies suggesting that the disease may be milder than elsewhere. This study aimed to describe CDI in Thailand, evaluate treatment options and their outcomes, as well as explore possible protective factors responsible for any unique disease characteristics. Between 2015 and 2018, 469 patients were included in the study. All patients had their stools tested for the tcdB gene by direct PCR and detection of toxigenic C. difficile by culture. C. difficile isolates were subjected to toxin gene profiling and ribotyping, and patient medical records were reviewed retrospectively. There were 248 and 221 patients included in CDI and control groups, respectively. The CDI group had a higher overall 30-day mortality rate than the control group (21% vs 14%, p = 0.046), but only 2 deaths (1%) were directly attributable to CDI. Metronidazole treatment was not inferior to vancomycin in this population and vancomycin was associated with a higher 30-day mortality rate (p = 0.047). The prevalence of severe CDI and disease outcomes were not different between patients infected with A-B+ C. difficile and A+B+ C. difficile strains, nor between patients with and without colonisation by non-toxigenic C. difficile. Besides C. difficile-specific tests, neither a single laboratory result nor a combination of results was predictive of CDI. In conclusion, CDI in Thailand was relatively mild and metronidazole remained an effective treatment option for these mild infections.

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Section: Discussionsupporting

confidence: 81%

Section: Discussioncontrasting

confidence: 52%

Mild or Malign: Clinical Characteristics and Outcomes of Clostridium difficile Infection in Thailand

et al. 2020

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“…Previous studies in addition to ours have shown that colonization with NTCD is effective in preventing CDI in animal models [13][14][15]. A surveillance study in two hospitals showed that in patients recently asymptomatically colonized with C. difficile (46% with a non-toxigenic strain) had a significantly lower incidence of CDI than patients who were in the same setting…”

Section: Discussionsupporting

confidence: 46%

Absence of toxin gene transfer from Clostridioides difficile strain 630Δerm to nontoxigenic C. difficile strain NTCD-M3r in filter mating experiments

et al. 2022

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Nontoxigenic Clostridioides difficile strain M3 (NTCD-M3) protects hamsters and humans against C. difficile infection. Transfer in vitro of the pathogenicity locus (PaLoc) to nontoxigenic strain CD37 has been reported. We repeated these conjugations using toxigenic strain 630Δerm as donor and NTCD-M3 and CD37 as recipients. In order to conduct these matings we induced rifampin resistance (50ug/ml) in NTCD-M3 by serial passage on rifampin-containing media to obtain strain NTCD-M3r. 630Δerm/CD37 matings produced 21 PaLoc transconjugants in 5.5 x 109 recipient CFUs; a frequency of 3.8 x 10−9. All transconjugants carried the tcdB gene and produced toxin. 630Δerm/NTCD-M3r matings produced no transconjugants in 5 assays with a total of 9.4 x 109 NTCD-M3r recipient cells. Toxin gene transfer to NTCD-M3r could not be demonstrated under conditions that demonstrated transfer to strain CD37.

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“…T7 with overexpressed CD0873 colonization factor effectively induced specific intestinal antibodies, which lowered the adhesion of pathogenic CD to Caco-2 cells. Another nontoxigenic CD strain named Z31 was used in piglets by Oliveira et al [ 61 ]. CD Z31, which was originally isolated from a healthy dog, was orally administered to piglets and effectively reduced CDI clinical signs and the occurrence of mesocolonic edema in piglets.…”

Section: Using Non-toxigenic Strainsmentioning

confidence: 99%

Non-Toxin-Based Clostridioides difficile Vaccination Approaches

2023

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Clostridioides difficile (CD) is a Gram-positive, anaerobic bacterium that infects mainly hospitalized and elderly people who have been treated with long-term antibiotic therapy leading to dysbiosis. The deteriorating demographic structure and the increase in the number of antibiotics used indicate that the problem of CD infections (CDI) will continue to increase. Thus far, there is no vaccine against CD on the market. Unfortunately, clinical trials conducted using the CD toxin-based antigens did not show sufficiently high efficacy, because they did not prevent colonization and transmission between patients. It seems that the vaccine should also include antigens found in the bacterium itself or its spores in order not only to fight the effects of toxins but also to prevent the colonization of the patient. This literature review summarizes the latest advances in research into vaccine antigens that do not contain CD toxins.

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The non-toxigenic strain of Clostridioides difficile Z31 can prevent infection by C. difficile in experimental model piglets

Cited by 9 publications

References 28 publications

Mild or Malign: Clinical Characteristics and Outcomes of Clostridium difficile Infection in Thailand

Mild or Malign: Clinical Characteristics and Outcomes of Clostridium difficile Infection in Thailand

Absence of toxin gene transfer from Clostridioides difficile strain 630Δerm to nontoxigenic C. difficile strain NTCD-M3r in filter mating experiments

Non-Toxin-Based Clostridioides difficile Vaccination Approaches

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