The CodY pleiotropic repressor controls virulence in gram-positive pathogens

Stenz, Ludwig; François, Patrice; Whiteson, Katrine; Wolz, Christiane; Linder, Patrick; Schrenzel, Jacques

doi:10.1111/j.1574-695x.2011.00812.x

Cited by 99 publications

(95 citation statements)

References 109 publications

(307 reference statements)

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“…The global regulatory protein CodY influences the expression of many metabolic and virulence genes in Gram-positive pathogens in response to the availability of GTP and the branched-chain amino acids (isoleucine, leucine, and valine) (8,9). In B. anthracis, CodY indirectly activates toxin gene expression, apparently by influencing AtxA stability (10,11).…”

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confidence: 99%

Identification of CodY Targets in Bacillus anthracis by Genome-Wide In Vitro Binding Analysis

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Schaik

Joseph

et al. 2013

Journal of Bacteriology

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confidence: 99%

Identification of CodY Targets in Bacillus anthracis by Genome-Wide In Vitro Binding Analysis

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Schaik

Joseph

et al. 2013

Journal of Bacteriology

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“…A nutritional regulator involved in the global control of amino acid metabolism in Gram-positive bacteria is CodY (67,71). It has been extensively studied in L. lactis (11,28) and other streptococci (8,39,40) and was reported to control the expression of hom, thrA, thrB, thrC, and cysD in these organisms.…”

Section: Resultsmentioning

confidence: 99%

Computational Analysis of Cysteine and Methionine Metabolism and Its Regulation in Dairy Starter and Related Bacteria

et al. 2012

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f Sulfuric volatile compounds derived from cysteine and methionine provide many dairy products with a characteristic odor and taste. To better understand and control the environmental dependencies of sulfuric volatile compound formation by the dairy starter bacteria, we have used the available genome sequence and experimental information to systematically evaluate the presence of the key enzymes and to reconstruct the general modes of transcription regulation for the corresponding genes. The genomic organization of the key genes is suggestive of a subdivision of the reaction network into five modules, where we observed distinct differences in the modular composition between the families Lactobacillaceae, Enterococcaceae, and Leuconostocaceae, on the one hand, and the family Streptococcaceae, on the other. These differences are mirrored by the way in which transcription regulation of the genes is structured in these families. In the Lactobacillaceae, Enterococcaceae, and Leuconostocaceae, the main shared mode of transcription regulation is methionine (Met) T-box-mediated regulation. In addition, the gene metK, Many of the characteristic flavors in fermented dairy products such as cheese and yoghurt are the result of metabolic reactions involving sulfur-containing amino acids. The microorganisms applied in these products degrade cysteine and methionine, resulting in the production of flavor components such as methanethiol, dimethyl sulfide (DMS), dimethyl disulfide (DMDS), and dimethyl trisulfide (DMTS). Insight into the regulatory signals and pathways that control the corresponding metabolic fluxes involved in the formation of these flavor compounds and their precursors is essential to rationally control and steer the flavor profiles of said dairy products.The microorganisms used to produce fermented dairy products belong to the taxonomic order Lactobacillales, which includes the families Enterococcaceae, Lactobacillaceae, Leuconostocaceae, and Streptococcaceae. Many of the respective species are characterized by the fact that they produce lactic acid and are therefore known as the lactic acid bacteria (LAB). The transcription of genes encoding the proteins that are involved in cysteine and methionine metabolism in lactic acid bacteria and other Lactobacillales is controlled by both regulator-binding and RNA structural switches. In various Streptococcaceae, the LysR-family transcription regulators MtaR and CmbR have been shown to be involved in activation as well as repression of genes such as cysD, cysK, metA, metC, metE, and metF (e.g., for Lactococcus lactis [25,70] and Streptococcus mutans [36,68]). The transcription regulator HomR was reported to control the expression of metB in S. mutans and Streptococcus thermophilus (69). In addition, three types of RNA structural switches for the regulation of cysteine and methionine metabolism have been reported for low-GC-content Grampositive bacteria: the T box, the S box, and the S MK box (14,22,59,77,80). These sequence elements at the 5= untranslated region of an...

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“…In pathogenic species, key virulence genes are also under CodY control (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). CodY can control transcription by binding in the vicinity of the promoter region of the target genes, by competing with a positive regulator for binding, or by serving as a roadblock to RNA polymerase (24).…”

Section: F Irst Identified In Bacillus Subtilismentioning

confidence: 99%

CodY Regulates Expression of the Bacillus subtilis Extracellular Proteases Vpr and Mpr

et al. 2015

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CodY is a global transcriptional regulator in low-G؉C Gram-positive bacteria that is responsive to GTP and branched-chain amino acids. By interacting with its two cofactors, it is able to sense the nutritional and energetic status of the cell and respond by regulating expression of adaptive genetic programs. In Bacillus subtilis, more than 200 genes, including those for peptide transporters, intracellular proteolytic enzymes, and amino acid degradative pathways, are controlled by CodY. In this study, we demonstrated that expression of two extracellular proteases, Vpr and Mpr, is negatively controlled by CodY. By gel mobility shift and DNase I footprinting assays, we showed that CodY binds to the regulatory regions of both genes, in the vicinity of their transcription start points. The mpr gene is also characterized by the presence of a second, higher-affinity CodY-binding site located at the beginning of its coding sequence. Using strains carrying vpr-or mpr-lacZ transcriptional fusions in which CodY-binding sites were mutated, we demonstrated that repression of both protease genes is due to the direct effect by CodY and that the mpr internal site is required for regulation. The vpr promoter is a rare example of a sigma H-dependent promoter that is regulated by CodY. In a codY null mutant, Vpr became one of the more abundant proteins of the B. subtilis exoproteome. IMPORTANCE CodY is a global transcriptional regulator of metabolism and virulence in low-G؉C

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The CodY pleiotropic repressor controls virulence in gram-positive pathogens

Cited by 99 publications

References 109 publications

Identification of CodY Targets in Bacillus anthracis by Genome-Wide In Vitro Binding Analysis

Identification of CodY Targets in Bacillus anthracis by Genome-Wide In Vitro Binding Analysis

Computational Analysis of Cysteine and Methionine Metabolism and Its Regulation in Dairy Starter and Related Bacteria

CodY Regulates Expression of the Bacillus subtilis Extracellular Proteases Vpr and Mpr

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