Anaerobe · 2026
A single clinical Clostridioides difficile RT012/ST54 isolate retains inflammatory activity under glucose-associated toxin-reducing conditions.
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Castro-Peña Carolina, Quesada-Gómez Carlos, Chaves-Olarte Esteban
Аннотация
INTRODUCTION: Clostridioides difficile infection is primarily attributed to toxin A (TcdA) and toxin B (TcdB), the major mediators of epithelial damage and intestinal inflammation. However, strain-dependent differences in pathogenicity have been reported, suggesting that additional bacterial factors may contribute to host inflammatory responses.
OBJECTIVE: To compare the inflammatory activity of culture supernatants from the single clinical isolate LIBA-5751/NAPCR1/RT012/ST54 and reference C. difficile strains under toxin-containing and glucose-repressed conditions.
METHODS: C. difficile strains, including the clinical isolates LIBA-5751/NAPCR1/RT012/ST54 and LIBA-5758/NAP1/RT027/ST01 and the reference strains VPI10463/RT003/ST046 and 630/RT012/ST54, were grown anaerobically in tryptose-yeast extract-thioglycolate broth with or without 1% glucose. Glucose-associated reduction of toxin activity was assessed by electrophoretic protein profiling, cytotoxicity assays, and Rac1 glucosylation analysis. Biological activity was evaluated in a mouse ligated ileal loop model by macroscopic examination, histopathology, cytokine quantification, and myeloperoxidase activity.
RESULTS: Glucose supplementation did not substantially alter bacterial growth but markedly reduced detectable toxin-associated bands, cytopathic activity, and Rac1 glucosylation. Toxin-containing supernatants from LIBA-5758/NAP1/RT027/ST01 and VPI10463/RT003/ST046 produced the most pronounced epithelial injury. Under the same conditions, LIBA-5758/NAP1/RT027/ST01, VPI10463/RT003/ST046, and LIBA-5751/NAPCR1/RT012/ST54 induced robust inflammatory responses. Under glucose-repressed conditions, epithelial damage was no longer evident, and inflammatory activity was markedly reduced in LIBA-5758/NAP1/RT027/ST01, VPI10463/RT003/ST046, and 630/RT012/ST54. In contrast, supernatants from LIBA-5751/NAPCR1/RT012/ST54 retained substantial inflammatory activity, including increased TNF-α, IL-1β, IL-6, and myeloperoxidase activity, despite the absence of overt epithelial damage.
CONCLUSIONS: The clinical isolate LIBA-5751/NAPCR1/RT012/ST54 retained substantial inflammatory activity under glucose-repressed conditions despite markedly reduced detectable toxin-associated activity. This phenotype was not observed to the same extent in the other strains examined, including the RT012/ST54 reference strain 630. These findings identify a strain-specific inflammatory phenotype observed in LIBA-5751/NAPCR1/RT012/ST54 and support further investigation into the extracellular factors that may contribute to inflammatory responses in C. difficile.
OBJECTIVE: To compare the inflammatory activity of culture supernatants from the single clinical isolate LIBA-5751/NAPCR1/RT012/ST54 and reference C. difficile strains under toxin-containing and glucose-repressed conditions.
METHODS: C. difficile strains, including the clinical isolates LIBA-5751/NAPCR1/RT012/ST54 and LIBA-5758/NAP1/RT027/ST01 and the reference strains VPI10463/RT003/ST046 and 630/RT012/ST54, were grown anaerobically in tryptose-yeast extract-thioglycolate broth with or without 1% glucose. Glucose-associated reduction of toxin activity was assessed by electrophoretic protein profiling, cytotoxicity assays, and Rac1 glucosylation analysis. Biological activity was evaluated in a mouse ligated ileal loop model by macroscopic examination, histopathology, cytokine quantification, and myeloperoxidase activity.
RESULTS: Glucose supplementation did not substantially alter bacterial growth but markedly reduced detectable toxin-associated bands, cytopathic activity, and Rac1 glucosylation. Toxin-containing supernatants from LIBA-5758/NAP1/RT027/ST01 and VPI10463/RT003/ST046 produced the most pronounced epithelial injury. Under the same conditions, LIBA-5758/NAP1/RT027/ST01, VPI10463/RT003/ST046, and LIBA-5751/NAPCR1/RT012/ST54 induced robust inflammatory responses. Under glucose-repressed conditions, epithelial damage was no longer evident, and inflammatory activity was markedly reduced in LIBA-5758/NAP1/RT027/ST01, VPI10463/RT003/ST046, and 630/RT012/ST54. In contrast, supernatants from LIBA-5751/NAPCR1/RT012/ST54 retained substantial inflammatory activity, including increased TNF-α, IL-1β, IL-6, and myeloperoxidase activity, despite the absence of overt epithelial damage.
CONCLUSIONS: The clinical isolate LIBA-5751/NAPCR1/RT012/ST54 retained substantial inflammatory activity under glucose-repressed conditions despite markedly reduced detectable toxin-associated activity. This phenotype was not observed to the same extent in the other strains examined, including the RT012/ST54 reference strain 630. These findings identify a strain-specific inflammatory phenotype observed in LIBA-5751/NAPCR1/RT012/ST54 and support further investigation into the extracellular factors that may contribute to inflammatory responses in C. difficile.