Toxicity assessment of Clostridium difficile toxins in rodent models and protection of vaccination

Wang, Su; Rustandi, Richard R.; Lancaster, Catherine; Hong, Laura; Thiriot, David S.; Xie, Jinfu; Secore, Susan; Kristopeit, Adam; Wang, Sheng‐Ching; Heinrichs, Jon H.

doi:10.1016/j.vaccine.2015.11.026

Cited by 14 publications

(8 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of fungi hyphae and conidia was frequent, and a good number of fungi could produce toxic compounds, and can even prove lethal [ 41 ]. Endospores of an unidentified Clostridium were also detected, and some species of this genus could also produce lethal compounds [ 44 ]. The proliferation on these organisms is probably related to inadequate microalgae biomass preservation after collection [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Are Cyanotoxins the Only Toxic Compound Potentially Present in Microalgae Supplements? Results from a Study of Ecological and Non-Ecological Products

Sánchez-Parra

Boutarfa

Aboal

2020

Toxins

View full text Add to dashboard Cite

Food supplements with microalgae are becoming increasingly abundant and can be easily found anywhere. The most popular products are based on cyanophytes, such as Aphanizomenon flos-aquae, Arthrospira platensis and Limnospira maxima, or on chlorophytes, such as Chlorella or Haematoccus. Although they are all advertised as being very beneficial for health, these products might be harmful because they may contain cyanotoxins and other contaminants, and no information on production methods or strain origins is usually provided. While legislation on the presence of microcystins in waters for different uses is clear, toxicological analyses are not compulsory for food supplements, nor for analyzing anatoxins. Given the potential risk of eating contaminated food, cyanotoxins, heavy metals and the presence of other contaminant organisms were analyzed in 10 microalgae food supplements. Microcystin-LR and anatoxin-a were detected in three analyzed products, and in both cyanophyte- and chlorophyte-based products. The light microscope study revealed the presence of different potentially harmful microbial contaminants. The ICP (OES) analyses detected high concentrations of some heavy metals, especially Pb. The results emphasize the need to promote the better control of food products containing microalgae, and to develop standard methodologies to analyze cyanotoxins and potential toxic compounds to protect consumer health.

show abstract

Section: Discussionmentioning

confidence: 99%

Are Cyanotoxins the Only Toxic Compound Potentially Present in Microalgae Supplements? Results from a Study of Ecological and Non-Ecological Products

Sánchez-Parra

Boutarfa

Aboal

2020

Toxins

View full text Add to dashboard Cite

show abstract

“…In non-outbreak situations, 17–23% of clinical isolates possess CDT genes [5,6]. Purified [7], and supernatant-derived CDT [8], are toxic to mammalian cell-lines, whilst purified CDT is also lethal in rodent models of C. difficile infection (CDI) [9]. Isogenic mutants of R20291 producing only CDT, were shown to cause symptomatic CDI in hamsters, in parallel, the co-expression of CDT, increases the virulence of mutants producing either TcdA, TcdB or both [10,11].…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation and functionality of CdtR in Clostridium difficile

2019

View full text Add to dashboard Cite

The production of TcdA, TcdB and CDT in Clostridium difficile PCR ribotype 027, is regulated by the two-component system response regulator CdtR. Despite this, little is known about the signal transduction pathway leading to the activation of CdtR. In this study, we generated R20291ΔPalocΔ cdtR model strains expressing CdtR phospho-variants in which our predicted phospho-accepting Asp, Asp61 was mutated for Ala or Glu. The constructs were assessed for their ability to restore CDT production. Dephospho-CdtR-Asp61Ala was completely non-functional and mirrored the cdtR -deletion mutant, whilst phospho-CdtR-Asp61Glu was functional, possessing 38–52% of wild-type activity. Taken together, these data suggest that CdtR is activated by phosphorylation of Asp61. The same principles were applied to assess the function of PCR ribotype 078-derived CdtR, which was shown to be non-functional owing to polymorphisms present within its coding gene. Conversely, polymorphisms present within its promoter region, provide significantly enhanced promoter activity compared with its PCR ribotype 027 counterpart. To ensure our data were representative for each ribotype, we determined that the cdtR nucleotide sequence was conserved in a small library of eight PCR ribotype 027 clinical isolates and nineteen PCR ribotype 078 isolates from clinical and animal origin.

show abstract

“… 1 In line with this new emerging trend, a vaccine candidate includes TcdA, TcdB, and components of C. difficile binary toxin CDT. 85 – 87 Similar to toxins A and B, CDT was shown to cause death in mice and hamsters, and the aforementioned combination vaccine approach protected mice when challenged with native toxins A, B, and CDT. 85 Unger et al 88 isolated llama sdAbs against CDTa and CDTb and found several sdAbs to neutralize cytotoxicity in vitro.…”

Section: Antibody-based Immunotherapiesmentioning

confidence: 99%

“… 85 – 87 Similar to toxins A and B, CDT was shown to cause death in mice and hamsters, and the aforementioned combination vaccine approach protected mice when challenged with native toxins A, B, and CDT. 85 Unger et al 88 isolated llama sdAbs against CDTa and CDTb and found several sdAbs to neutralize cytotoxicity in vitro. As the antitoxin antibodies do not prevent the initial C. difficile colonization step, complementing them with antibodies that target spores and prevent or eliminate their carriage or dissemination appears attractive.…”

Section: Antibody-based Immunotherapiesmentioning

confidence: 99%

An update on antibody-based immunotherapies for <em>Clostridium difficile</em> infection

Hussack¹,

Tanha²

2016

CEG

View full text Add to dashboard Cite

Clostridium difficile continues to be one of the most prevalent hospital-acquired bacterial infections in the developed world, despite the recent introduction of a novel and effective antibiotic agent (fidaxomicin). Alternative approaches under investigation to combat the anaerobic Gram-positive bacteria include fecal transplantation therapy, vaccines, and antibody-based immunotherapies. In this review, we catalog the recent advances in antibody-based approaches under development and in the clinic for the treatment of C. difficile infection. By and large, inhibitory antibodies that recognize the primary C. difficile virulence factors, toxin A and toxin B, are the most popular passive immunotherapies under investigation. We provide a detailed summary of the toxin epitopes recognized by various antitoxin antibodies and discuss general trends on toxin inhibition efficacy. In addition, antibodies to other C. difficile targets, such as surface-layer proteins, binary toxin, motility factors, and adherence and colonization factors, are introduced in this review.

show abstract

Toxicity assessment of Clostridium difficile toxins in rodent models and protection of vaccination

Cited by 14 publications

References 22 publications

Are Cyanotoxins the Only Toxic Compound Potentially Present in Microalgae Supplements? Results from a Study of Ecological and Non-Ecological Products

Are Cyanotoxins the Only Toxic Compound Potentially Present in Microalgae Supplements? Results from a Study of Ecological and Non-Ecological Products

Phosphorylation and functionality of CdtR in Clostridium difficile

An update on antibody-based immunotherapies for <em>Clostridium difficile</em> infection

Contact Info

Product

Resources

About