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J Med Microbiol 57 (2008), 757-764; DOI: 10.1099/jmm.0.47657-0
© 2008 Society for General Microbiology
ISSN 1473-5644

Microarray analysis of the transcriptional responses of Clostridium difficile to environmental and antibiotic stress

Jenny E. Emerson1, Richard A. Stabler2, Brendan W. Wren2 and Neil F. Fairweather1

1 Centre for Molecular Microbiology and Infection, Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, UK

2 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

Correspondence
Neil F. Fairweather
n.fairweather{at}imperial.ac.uk

Received 27 September 2007
Accepted 25 January 2008

Clostridium difficile is a spore-forming anaerobic bacterium that is an emerging nosocomial threat; incidence of infection in hospitals is increasing, both in frequency and severity, resulting in considerable morbidity and mortality. In order to adapt to the intestinal environment, C. difficile must react to the many stresses involved with colonization, including exposure to antibiotics, which represents the most frequent precipitating agent of C. difficile infection. The responses of C. difficile to environmental shocks (heat, pH and oxidative shock) and to growth in the presence of subinhibitory concentrations of antibiotics (amoxicillin, clindamycin and metronidazole) were investigated using the C. difficile 630 microarray developed by the Bacterial Microarray Group at St George's, University of London, UK ( µG@S). Significantly regulated genes and operons were identified that are unique to or common between different stresses. The transcriptional profiles of C. difficile 630 are similar after growth in the presence of amoxicillin and clindamycin: both increased transcription of ribosomal protein genes and altered transcription of genes encoding surface-associated proteins. In contrast, metronidazole treatment resulted in minor changes in transcription patterns. The general stress response is observed after heat shock and acid shock. Heat shock also affected transcription of several biochemical pathways. Exposure to atmospheric oxygen induced a large number of electron transporters. This study provides a starting point for detailed analyses of numerous genes whose expression is affected by stress and may therefore be involved in adaptation to the host environment.

Abbreviations: CDAD, Clostridium difficile-associated disease; CWP, cell wall protein.

Fully annotated microarray data are available in µG@Sbase (http://bugs.sgul.ac.uk) and also ArrayExpress (http://www.ebi.ac.uk/arrayexpress/) with accession numbers E-BUGS-55 (environmental shock) and E-BUGS-56 (growth in the presence of antibiotics).

Tables of gene expression data are available as supplementary data with the online version of this paper.




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