title: HosA, a MarR Family Transcriptional Regulator, Represses Nonoxidative Hydroxyarylic Acid Decarboxylase Operon and Is Modulated by 4-Hydroxybenzoic Acid.
abstract: Members of the Multiple antibiotic resistance Regulator (MarR) family of DNA binding proteins regulate transcription of a wide array of genes required for virulence and pathogenicity of bacteria. The present study reports the molecular characterization of HosA (Homologue of SlyA), a MarR protein, with respect to its target gene, DNA recognition motif, and nature of its ligand. Through a comparative genomics approach, we demonstrate that hosA is in synteny with nonoxidative hydroxyarylic acid decarboxylase (HAD) operon and is present exclusively within the mutS-rpoS polymorphic region in nine different genera of Enterobacteriaceae family. Using molecular biology and biochemical approach, we demonstrate that HosA binds to a palindromic sequence downstream to the transcription start site of divergently transcribed nonoxidative HAD operon and represses its expression. Furthermore, in silico analysis showed that the recognition motif for HosA is highly conserved in the upstream region of divergently transcribed operon in different genera of Enterobacteriaceae family. A systematic chemical search for the physiological ligand revealed that 4-hydroxybenzoic acid (4-HBA) interacts with HosA and derepresses HosA mediated repression of the nonoxidative HAD operon. Based on our study, we propose a model for molecular mechanism underlying the regulation of nonoxidative HAD operon by HosA in Enterobacteriaceae family.
authors.affiliation: Computational and Functional Genomics Group, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana 500001, India.|Graduate studies, Manipal University , Manipal 576104, India.
authors.forename: Ajit
authors.initials: A
authors.lastname: Roy
authors.affiliation: Computational and Functional Genomics Group, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana 500001, India.
authors.forename: Akash
authors.initials: A
authors.lastname: Ranjan
mesh_terms: D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D018983:DNA Footprinting; D004794:Enzyme Repression; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005103:Expert Systems; D008024:Ligands; D008954:Models, Biological; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D059372:Nucleotide Motifs; D009876:Operon; D010226:Parabens / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D026801:Synteny; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056689:Uropathogenic Escherichia coli / Q000201:enzymology / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C498398:HosA protein, E coli; D008024:Ligands; D010226:Parabens; D011994:Recombinant Proteins; D014157:Transcription Factors; D002262:Carboxy-Lyases; C038193:4-hydroxybenzoic acid