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A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment
Published on: May 25, 2017
Antibiotics involved in Clostridium difficile-associated disease increase colonization factor gene expression
Cécile Denève1, Claudine Deloménie2, Marie-Claude Barc1
1Université Paris Sud-XI, USC INRA 4043, Faculté de Pharmacie, Châtenay-Malabry, France.
Journal of Medical Microbiology
|May 16, 2008
Summary
Certain antibiotics like ampicillin and clindamycin may increase Clostridium difficile infection risk by boosting its colonization factors and adherence. This direct effect complements their known disruption of gut microbiota.
Area of Science:
- Microbiology
- Infectious Diseases
- Molecular Biology
Background:
- Clostridium difficile is a leading cause of antibiotic-associated diarrhea.
- Antibiotics disrupt intestinal microbiota, potentially enabling C. difficile colonization and adherence.
- Understanding C. difficile colonization factors and their regulation is crucial for infection control.
Purpose of the Study:
- To investigate the in vitro impact of environmental conditions on C. difficile colonization factor gene expression.
- To determine the effect of specific antibiotics (ampicillin, clindamycin, ofloxacin, moxifloxacin, kanamycin) on gene expression and bacterial adherence.
- To compare responses across toxigenic and non-toxigenic C. difficile strains.
Main Methods:
- Real-time PCR was used to analyze the expression of genes encoding adhesins (P47, Cwp66, Fbp68) and a protease (Cwp84).
- C. difficile isolates were exposed to subinhibitory concentrations (1/2 MIC) of various antibiotics and other conditions (hyperosmolarity, iron depletion).
- Adherence assays were performed using Caco-2/TC7 cells to assess bacterial attachment.
Main Results:
- Exposure to subinhibitory concentrations of ampicillin and clindamycin significantly increased the expression of colonization factor genes in all six C. difficile strains studied.
- This increased gene expression correlated with enhanced adherence of C. difficile to cultured intestinal cells.
- Ofloxacin, moxifloxacin, and kanamycin showed minimal or no significant effect on the expression of these genes.
Conclusions:
- Ampicillin and clindamycin may directly promote C. difficile colonization by upregulating virulence factors and enhancing bacterial adherence.
- These findings provide a potential mechanism beyond microbiota disruption for the increased risk of C. difficile infection associated with these antibiotics.
- The study highlights the importance of considering direct antibiotic effects on pathogen virulence in understanding infection dynamics.
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