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Background  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.    Results  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.    Conclusion  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.

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