Open Access Highly Accessed Research article

Global regulation of gene expression in response to cysteine availability in Clostridium perfringens

Gaelle André12, Elise Haudecoeur1234, Marc Monot3, Kaori Ohtani5, Tohru Shimizu5, Bruno Dupuy3 and Isabelle Martin-Verstraete1234*

Author Affiliations

1 Institut Pasteur, Unité de Génétique des Génomes Bactériens and Unité des Bactéries Anaérobies et Toxines, 28 rue du Docteur Roux, 75015 Paris, France

2 CNRS URA 2171, 75015 Paris, France

3 Institut Pasteur, Laboratoire de Pathogénèse des Bactéries Anaérobies, 28 rue du Docteur Roux, 75015 Paris, France

4 Université Paris 7-Denis Diderot, 75205 Paris, France

5 Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, Ishikawa, 920-8640 Japan

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BMC Microbiology 2010, 10:234  doi:10.1186/1471-2180-10-234

Published: 7 September 2010



Cysteine has a crucial role in cellular physiology and its synthesis is tightly controlled due to its reactivity. However, little is known about the sulfur metabolism and its regulation in clostridia compared with other firmicutes. In Clostridium perfringens, the two-component system, VirR/VirS, controls the expression of the ubiG operon involved in methionine to cysteine conversion in addition to the expression of several toxin genes. The existence of links between the C. perfringens virulence regulon and sulfur metabolism prompted us to analyze this metabolism in more detail.


We first performed a tentative reconstruction of sulfur metabolism in C. perfringens and correlated these data with the growth of strain 13 in the presence of various sulfur sources. Surprisingly, C. perfringens can convert cysteine to methionine by an atypical still uncharacterized pathway. We further compared the expression profiles of strain 13 after growth in the presence of cystine or homocysteine that corresponds to conditions of cysteine depletion. Among the 177 genes differentially expressed, we found genes involved in sulfur metabolism and controlled by premature termination of transcription via a cysteine specific T-box system (cysK-cysE, cysP1 and cysP2) or an S-box riboswitch (metK and metT). We also showed that the ubiG operon was submitted to a triple regulation by cysteine availability via a T-box system, by the VirR/VirS system via the VR-RNA and by the VirX regulatory RNA.

In addition, we found that expression of pfoA (theta-toxin), nagL (one of the five genes encoding hyaluronidases) and genes involved in the maintenance of cell redox status was differentially expressed in response to cysteine availability. Finally, we showed that the expression of genes involved in [Fe-S] clusters biogenesis and of the ldh gene encoding the lactate dehydrogenase was induced during cysteine limitation.


Several key functions for the cellular physiology of this anaerobic bacterium were controlled in response to cysteine availability. While most of the genes involved in sulfur metabolism are regulated by premature termination of transcription, other still uncharacterized mechanisms of regulation participated in the induction of gene expression during cysteine starvation.