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18 Jan 2013

Characterization of a Stable, Metronidazole-Resistant Clostridium difficile Clinical Isolate (PLoS ONE, abstract, edited)

[Source: PLoS ONE, full page: (LINK). Abstract, edited.]

Research Article

Characterization of a Stable, Metronidazole-Resistant Clostridium difficile Clinical Isolate

Tarah Lynch, Patrick Chong, Jason Zhang, Romeo Hizon, Tim Du, Morag R. Graham, Daniel R. Beniac, Timothy F. Booth, Pamela Kibsey, Mark Miller, Denise Gravel, Michael R. Mulvey

Affiliation: [Full list on source page.]




Clostridium difficile are Gram-positive, spore forming anaerobic bacteria that are the leading cause of healthcare-associated diarrhea, usually associated with antibiotic usage. Metronidazole is currently the first-line treatment for mild to moderate C. difficile diarrhea however recurrence occurs at rates of 15–35%. There are few reports of C. difficile metronidazole resistance in the literature, and when observed, the phenotype has been transient and lost after storage or exposure of the bacteria to freeze/thaw cycles. Owing to the unstable nature of the resistance phenotype in the laboratory, clinical significance and understanding of the resistance mechanisms is lacking.

Methodology/Principal Findings

Genotypic and phenotypic characterization was performed on a metronidazole resistant clinical isolate of C. difficile. Whole-genome sequencing was used to identify potential genetic contributions to the phenotypic variation observed with molecular and bacteriological techniques. Phenotypic observations of the metronidazole resistant strain revealed aberrant growth in broth and elongated cell morphology relative to a metronidazole-susceptible, wild type NAP1 strain. Comparative genomic analysis revealed single nucleotide polymorphism (SNP) level variation within genes affecting core metabolic pathways such as electron transport, iron utilization and energy production.


This is the first characterization of stable, metronidazole resistance in a C. difficile isolate. The study provides an in-depth genomic and phenotypic analysis of this strain and provides a foundation for future studies to elucidate mechanisms conferring metronidazole resistance in C. difficile that have not been previously described.


Citation: Lynch T, Chong P, Zhang J, Hizon R, Du T, et al. (2013) Characterization of a Stable, Metronidazole-Resistant Clostridium difficile Clinical Isolate. PLoS ONE 8(1): e53757. doi:10.1371/journal.pone.0053757

Editor: Axel Cloeckaert, Institut National de la Recherche Agronomique, France

Received: September 5, 2012; Accepted: December 4, 2012; Published: January 17, 2013

Copyright: © 2013 Lynch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: No external funding sources were received for this study. This project was funded solely by the Public Health Agency of Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

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¶ Membership of the Canadian Nosocomial Infection Surveillance Program (CNISP) is provided in the Acknowledgments.