Non-Toxigenic Clostridioides difficile Strain E4 (NTCD-E4) Prevents Establishment of Primary C. difficile Infection by Epidemic PCR Ribotype 027 in an In Vitro Human Gut Model
Clostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human recurrent CDI. In this study, we evaluated the efficacy of metronidazole-resistant NTCD-E4 in preventing CDI facilitated by a range of antimicrobials in an in vitro human gut model. NTCD-E4 spores (at a dose of 107) were instilled 7 days before a clinical ribotype (RT) 027 (at the same dose) strain (210). In separate experiments, four different antimicrobials were used to perturb gut microbiotas; bacterial populations and cytotoxin production were determined using viable counting and Vero cell cytotoxicity, respectively. RT027 and NTCD-E4 proliferated in the in vitro model when inoculated singly, with RT027 demonstrating high-level cytotoxin (3-5-log10-relative units) production. In experiments where the gut model was pre-inoculated with NTCD-E4, RT027 was remained quiescent and failed to produce cytotoxins. NTCD-E4 showed mutations in hsmA and a gene homologous to CD196-1331, previously linked to medium-dependent metronidazole resistance, but lacked other metronidazole resistance determinants. This study showed that RT027 was unable to elicit simulated infection in the presence of NTCD-E4 following stimulation by four different antimicrobials. These data complement animal and clinical studies in suggesting NTCD offer prophylactic potential in the management of human CDI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Antibiotics (Basel, Switzerland) - 12(2023), 3 vom: 22. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Etifa, Perezimor [VerfasserIn] |
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| Links: |
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| Themen: |
Antibiotics |
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| Anmerkungen: |
Date Revised 31.03.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/antibiotics12030435 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM354832654 |
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| 520 | |a Clostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human recurrent CDI. In this study, we evaluated the efficacy of metronidazole-resistant NTCD-E4 in preventing CDI facilitated by a range of antimicrobials in an in vitro human gut model. NTCD-E4 spores (at a dose of 107) were instilled 7 days before a clinical ribotype (RT) 027 (at the same dose) strain (210). In separate experiments, four different antimicrobials were used to perturb gut microbiotas; bacterial populations and cytotoxin production were determined using viable counting and Vero cell cytotoxicity, respectively. RT027 and NTCD-E4 proliferated in the in vitro model when inoculated singly, with RT027 demonstrating high-level cytotoxin (3-5-log10-relative units) production. In experiments where the gut model was pre-inoculated with NTCD-E4, RT027 was remained quiescent and failed to produce cytotoxins. NTCD-E4 showed mutations in hsmA and a gene homologous to CD196-1331, previously linked to medium-dependent metronidazole resistance, but lacked other metronidazole resistance determinants. This study showed that RT027 was unable to elicit simulated infection in the presence of NTCD-E4 following stimulation by four different antimicrobials. These data complement animal and clinical studies in suggesting NTCD offer prophylactic potential in the management of human CDI | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Sidorov, Igor A |e verfasserin |4 aut | |
| 700 | 1 | |a Mohammed, Olufunmilayo A |e verfasserin |4 aut | |
| 700 | 1 | |a Savage, Emily |e verfasserin |4 aut | |
| 700 | 1 | |a Timms, Andrew R |e verfasserin |4 aut | |
| 700 | 1 | |a Freeman, Jane |e verfasserin |4 aut | |
| 700 | 1 | |a Smits, Wiep Klaas |e verfasserin |4 aut | |
| 700 | 1 | |a Wilcox, Mark H |e verfasserin |4 aut | |
| 700 | 1 | |a Baines, Simon D |e verfasserin |4 aut | |
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