Prevention of Clostridium difficile-induced experimental pseudomembranous colitis by Saccharomyces boulardii: a scanning electron microscopic and microbiological study

Castex, Françoise; Corthier, Gérard; Jouvert, S.; Elmer, Gary W.; Lucas, François; Bastide, M.

doi:10.1099/00221287-136-6-1085

Cited by 42 publications

(22 citation statements)

References 17 publications

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“…5). This protective effect against C. difficile has already been observed by many authors utilizing S. boulardii (Castagliuolo et al, 1996;Castex et al, 1990;Corthier et al, 1986Corthier et al, , 1992Czerucka et al, 1991;Elmer and Corthier, 1991;Pothoulakis et al, 1993) and a strain of S. cerevisiae (Izadnia et al, 1998). Antagonism by inhibitory compound production is one of the hypothesis more frequently used to explain probiotic acts against enteropathogenic microorganisms.…”

Section: Discussionsupporting

confidence: 61%

Screening of yeasts as probiotic based on capacities to colonize the gastrointestinal tract and to protect against enteropathogen challenge in mice

Martins

Nardi

Arantes

et al. 2005

J. Gen. Appl. Microbiol.

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Section: Discussionsupporting

confidence: 61%

Screening of yeasts as probiotic based on capacities to colonize the gastrointestinal tract and to protect against enteropathogen challenge in mice

Martins

Nardi

Arantes

et al. 2005

J. Gen. Appl. Microbiol.

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“…As shown by a previous report, live S.b is effective in protecting from C. difficile infection in hamsters (5). To establish this model in our laboratory, we administered clindamycin via oral gavage 5 days before C. difficile inoculation as suggested by a previous report (10).…”

Section: Live But Not Heated S Boulardii Significantly Inhibited Cmentioning

confidence: 99%

ProbioticSaccharomyces boulardiiCNCM I-745 prevents outbreak-associatedClostridium difficile-associated cecal inflammation in hamsters

Koon

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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. difficile infection (CDI) is a common debilitating nosocomial infection associated with high mortality. Several CDI outbreaks have been attributed to ribotypes 027, 017, and 078. Clinical and experimental evidence indicates that the nonpathogenic yeast Saccharomyces boulardii CNCM I-745 (S.b) is effective for the prevention of CDI. However, there is no current evidence suggesting this probiotic can protect from CDI caused by outbreak-associated strains. We used established hamster models infected with outbreak-associated C. difficile strains to determine whether oral administration of live or heat-inactivated S.b can prevent cecal tissue damage and inflammation. Hamsters infected with C. difficile strain VPI10463 (ribotype 087) and outbreakassociated strains ribotype 017, 027, and 078 developed severe cecal inflammation with mucosal damage, neutrophil infiltration, edema, increased NF-B phosphorylation, and increased proinflammatory cytokine TNF␣ protein expression. Oral gavage of live, but not heated, S.b starting 5 days before C. difficile infection significantly reduced cecal tissue damage, NF-B phosphorylation, and TNF␣ protein expression caused by infection with all strains. Moreover, S.b-conditioned medium reduced cell rounding caused by filtered supernatants from all C. difficile strains. S.b-conditioned medium also inhibited toxin A-and B-mediated actin cytoskeleton disruption. S.b is effective in preventing C. difficile infection by outbreak-associated via inhibition of the cytotoxic effects of C. difficile toxins. (46). C. difficile is an anaerobic bacterium that produces two toxins -toxin A and toxin B -that mediate diarrhea, inflammation, and apoptosis of the mucosal epithelium in animals and humans (32). The effects of the toxin in target intestinal cells involve inactivation of the Rho family of GTPase, leading to cytoskeletal disorganization, epithelial cell apoptosis, and ultimately cell death (42, 54). C. difficile toxins also stimulate transcription of several proinflammatory genes, including tumor necrosis factor-␣ (TNF␣) (19) and activate transcription factors and mitogen-activated protein kinases involved in their proinflammatory effects (18,25). The mainstream CDI regimen includes the use of metronidazole, vancomycin, and fidaxomicin (55). However, many C. difficileinfected patients may also suffer from recurrent infections (13), while the recent epidemics that also involve new epidemic outbreak-associated strains (29) pose a major medical problem and epidemiological concern. These challenges have been met with a broad range of preventive approaches against CDI, including the use of probiotics, most notably Saccharomyces boulardii (S.b) alone or in combination with established antibiotic treatment (23,24).S.b is a nonpathogenic yeast that represents one of the well-studied probiotics against CDI in both experimental and clinical settings (24,40). Randomized double-blind placebocontrolled clinical trials have shown that S.b CNCM I-745 is an effective probiotic in the prophylaxis of antibi...

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“…C. difficile toxins, for example, cause cellular toxicity through the glucosylation of Rho G-protein and ADP-ribosylation of actin, while C. diphtheriae and P. aeruginosa toxins catalyze the transfer of ADP-ribose to elongation factor 2 to block host cell protein synthesis, leading to the death of their target cells (5)(6)(7)(8). The clostridial toxin TcdB of C. difficile inactivates the small GTPases Rho, Rac, and Cdc42, which have been shown to trigger cell death via apoptosis (2,(9)(10)(11).…”

mentioning

confidence: 99%

Caspase Activation as a Versatile Assay Platform for Detection of Cytotoxic Bacterial Toxins

et al. 2013

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Pathogenic bacteria produce several virulence factors that help them establish infection in permissive hosts. Bacterial toxins are a major class of virulence factors and hence are attractive therapeutic targets for vaccine development. Here, we describe the development of a rapid, sensitive, and high-throughput assay that can be used as a versatile platform to measure the activities of bacterial toxins. We have exploited the ability of these toxins to cause cell death via apoptosis of sensitive cultured cell lines as a readout for measuring toxin activity. Caspases (cysteine-aspartic proteases) are induced early in the apoptotic pathway, and so we used their induction to measure the activities of Clostridium difficile toxins A (TcdA) and B (TcdB) and binary toxin (CDTaCDTb), Corynebacterium diphtheriae toxin (DT), and Pseudomonas aeruginosa exotoxin A (PEA). Caspase induction in the cell lines, upon exposure to toxins, was optimized by toxin concentration and intoxication time, and the specificity of caspase activity was established using a genetically mutated toxin and a pan-caspase inhibitor. In addition, we demonstrate the utility of the caspase assay for measuring toxin potency, as well as neutralizing antibody (NAb) activity against C. difficile toxins. Furthermore, the caspase assay showed excellent correlation with the filamentous actin (F-actin) polymerization assay for measuring TcdA and TcdB neutralization titers upon vaccination of hamsters. These results demonstrate that the detection of caspase induction due to toxin exposure using a chemiluminescence readout can support potency and clinical immunogenicity testing for bacterial toxin vaccine candidates in development.

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Prevention of Clostridium difficile-induced experimental pseudomembranous colitis by Saccharomyces boulardii: a scanning electron microscopic and microbiological study

Cited by 42 publications

References 17 publications

Screening of yeasts as probiotic based on capacities to colonize the gastrointestinal tract and to protect against enteropathogen challenge in mice

Screening of yeasts as probiotic based on capacities to colonize the gastrointestinal tract and to protect against enteropathogen challenge in mice

ProbioticSaccharomyces boulardiiCNCM I-745 prevents outbreak-associatedClostridium difficile-associated cecal inflammation in hamsters

Caspase Activation as a Versatile Assay Platform for Detection of Cytotoxic Bacterial Toxins

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