Persistent URL of this record https://hdl.handle.net/1887/3665520
Documents
-
- Download
- antibiotics-12-00435-v3-1
- Publisher's Version
- open access
- Full text at publishers site
In Collections
This item can be found in the following collections:
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
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...Show moreClostridioides 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.
Show less
- All authors
- Etifa, P.; Rodríguez, C.; Harmanus, C.; Sanders, I.M.J.G.; Sidorov, I.A.; Mohammed, O.A.; Savage, E.; Timms, A.R.; Freeman, J.; Smits, W.K.; Wilcox, M.H.; Baines, S.D.
- Date
- 2023-03-01
- Journal
- Antibiotics
- Volume
- 12
- Issue
- 3