{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sonnleitner E"],"funding":["Wellcome Trust"],"pagination":["1195558"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10213629"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14"],"pubmed_abstract":["In the opportunistic human pathogen <i>Pseudomonas aeruginosa</i> (<i>Pae</i>), <i>c</i>arbon <i>c</i>atabolite <i>r</i>epression (CCR) orchestrates the hierarchical utilization of N and C sources, and impacts virulence, antibiotic resistance and biofilm development. During CCR, the RNA chaperone Hfq and the <i>c</i>atabolite <i>r</i>epression <i>c</i>ontrol protein Crc form assemblies on target mRNAs that impede translation of proteins involved in uptake and catabolism of less preferred C sources. After exhaustion of the preferred C-source, translational repression of target genes is relieved by the regulatory RNA CrcZ, which binds to and acts as a decoy for Hfq. Here, we asked whether Crc action can be modulated to relieve CCR after exhaustion of a preferred carbon source. As Crc does not bind to RNA <i>per se</i>, we endeavored to identify an interacting protein. <i>In vivo</i> co-purification studies, co-immunoprecipitation and biophysical assays revealed that Crc binds to <i>Pae</i> strain O1 protein PA1677. Our structural studies support bioinformatics analyzes showing that PA1677 belongs to the isochorismatase-like superfamily. Ectopic expression of PA<i>1677</i> resulted in de-repression of Hfq/Crc controlled target genes, while in the absence of the protein, an extended lag phase is observed during diauxic growth on a preferred and a non-preferred carbon source. This observations indicate that PA1677 acts as an antagonist of Crc that favors synthesis of proteins required to metabolize non-preferred carbon sources. We present a working model wherein PA1677 diminishes the formation of productive Hfq/Crc repressive complexes on target mRNAs by titrating Crc. Accordingly, we propose the name CrcA (<i>c</i>atabolite <i>r</i>epression <i>c</i>ontrol protein <i>a</i>ntagonist) for PA1677."],"journal":["Frontiers in microbiology"],"pubmed_title":["Catabolite repression control protein antagonist, a novel player in <i>Pseudomonas aeruginosa</i> carbon catabolite repression control."],"pmcid":["PMC10213629"],"funding_grant_id":["200873/Z/16/Z"],"pubmed_authors":["Blasi U","Lilic B","Brear P","Sonnleitner E","Bassani F","Cianciulli Sesso A","Luisi BF","Davidovski L","Resch A","Moll I"],"additional_accession":[]},"is_claimable":false,"name":"Catabolite repression control protein antagonist, a novel player in <i>Pseudomonas aeruginosa</i> carbon catabolite repression control.","description":"In the opportunistic human pathogen <i>Pseudomonas aeruginosa</i> (<i>Pae</i>), <i>c</i>arbon <i>c</i>atabolite <i>r</i>epression (CCR) orchestrates the hierarchical utilization of N and C sources, and impacts virulence, antibiotic resistance and biofilm development. During CCR, the RNA chaperone Hfq and the <i>c</i>atabolite <i>r</i>epression <i>c</i>ontrol protein Crc form assemblies on target mRNAs that impede translation of proteins involved in uptake and catabolism of less preferred C sources. After exhaustion of the preferred C-source, translational repression of target genes is relieved by the regulatory RNA CrcZ, which binds to and acts as a decoy for Hfq. Here, we asked whether Crc action can be modulated to relieve CCR after exhaustion of a preferred carbon source. As Crc does not bind to RNA <i>per se</i>, we endeavored to identify an interacting protein. <i>In vivo</i> co-purification studies, co-immunoprecipitation and biophysical assays revealed that Crc binds to <i>Pae</i> strain O1 protein PA1677. Our structural studies support bioinformatics analyzes showing that PA1677 belongs to the isochorismatase-like superfamily. Ectopic expression of PA<i>1677</i> resulted in de-repression of Hfq/Crc controlled target genes, while in the absence of the protein, an extended lag phase is observed during diauxic growth on a preferred and a non-preferred carbon source. This observations indicate that PA1677 acts as an antagonist of Crc that favors synthesis of proteins required to metabolize non-preferred carbon sources. We present a working model wherein PA1677 diminishes the formation of productive Hfq/Crc repressive complexes on target mRNAs by titrating Crc. Accordingly, we propose the name CrcA (<i>c</i>atabolite <i>r</i>epression <i>c</i>ontrol protein <i>a</i>ntagonist) for PA1677.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023","modification":"2026-05-28T22:50:25.819Z","creation":"2025-04-06T00:49:32.092Z"},"accession":"S-EPMC10213629","cross_references":{"pubmed":["37250041"],"doi":["10.3389/fmicb.2023.1195558"]}}