By contrast, the asrABC1 and asrABC2 operons as well as the pepT and pepM genes (Fig. 1) were not differentially expressed after growth in the presence of homocysteine or cystine. The synthesis of SB431542 molecular weight sulfite reductases may be induced in the presence of sulfite as shown for

Clostridium pasterianum [49]. In the absence of sulfite in the growth medium, we do not observe any regulation for the asr operons by the sulfur sources tested. Among the genes differentially expressed during cysteine depletion, we were also unable to identify candidates for methionine biosynthesis. The enzymes involved could be either mTOR inhibitor constitutively synthesized or the effector modulating the transcription of the corresponding genes is not sufficiently depleted under the growth conditions tested. Control of iron-sulfur cluster biogenesis and related functions Expression of genes involved in [Fe-S] cluster biogenesis was regulated in response to cysteine availability (Table 1). Actually,

four genes adjacent on the chromosome, cpe1783 to cpe1786, were up-regulated 3 to 6-fold during cysteine limitation. Cpe1786 is a repressor of the Rrf2 family sharing 50% identity with CymR, the global regulator of cysteine metabolism of B. subtilis [16] and 37% with IscR, the regulator of [Fe-S] cluster biogenesis in E. coli [50]. Cpe1785 and Cpe1784 encode a cysteine desulfurase and a scaffold protein for [Fe-S] cluster assembly, respectively [1] while TrmU (Cpe1783) is an enzyme involved in thio-uridylation of tRNAs. In the absence of nitrogen fixation in C. perfringens, we proposed to rename cpe1785, iscS instead of nifS and cpe1784, iscU instead SRT1720 clinical trial of nifU. The expression of cpe1469 encoding a putative cysteine desulfurase sharing 25% identity with IscS also increased during cysteine

depletion. Finally, the expression of cpe0664 encoding a 114 amino-acid protein, which corresponds to an A-type carrier required for [Fe-S] cluster assembly filipin [51], was induced during cysteine limitation (Table 1). Thus, in the absence of the suf genes in C. perfringens, iscSU and cpe0664 probably constitute the unique system of [Fe-S] cluster biogenesis in this bacterium [1]. In E. coli and several other bacteria, genes involved in this process are regulated in response to [Fe-S] availability via the [Fe-S] protein IscR, and are induced during iron starvation and oxidative stress [1, 52]. By contrast, only few data are available concerning the control of [Fe-S] cluster synthesis by cysteine availability. The coordinated derepression of genes involved in [Fe-S] production (cpe1785, cpe1784, cpe1469, cpe0664) during cysteine depletion may allow C. perfringens maintaining its pools of [Fe-S] clusters, which play a crucial role in the physiology of these bacteria lacking the heme synthesis machinery [53]. Expression of ldh encoding the lactate dehydrogenase (LDH) increased 2.