title: Reduced synthesis of the Ybt siderophore or production of aberrant Ybt-like molecules activates transcription of yersiniabactin genes in Yersinia pestis.
abstract: Synthesis of the siderophore yersiniabactin (Ybt) proceeds by a mixed nonribosomal peptide synthetase/polyketide synthase mechanism. Transcription of ybt genes encoding biosynthetic and transport functions is repressed under excess iron conditions by Fur, but is also activated by Ybt via the transcriptional regulator YbtA. While mutations in most biosynthetic genes and ybtA negate transcription activation from the regulated promoters, three biosynthetic mutations do not reduce this transcriptional activation. Here we show that two of these mutants, one lacking the putative type II thioesterase (TE) YbtT and the other with a mutation in the TE domain of HMWP1, produce reduced levels of authentic Ybt that are capable of signalling activity. Alanine substitutions in two residues of YbtT that are essential for catalytic activity in other type II TEs reduced the ability of Yersinia pestis to grow under iron-chelated conditions. The third mutant, which lacks the salicylate synthase YbtS, did not make authentic Ybt but did produce a signalling molecule. Finally, a Delta pgm strain of Y. pestis, which lacks essential Ybt biosynthetic genes, also produced a signalling molecule that can activate transcription of ybt genes. The non-Ybt signal molecules from these two mutants are likely separate compounds. While these compounds are not biologically relevant to normal Ybt regulation, a comparison of the structures of Ybt and other signalling molecules will help in determining the chemical structures recognized as a Ybt signal.
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.
authors.forename: M Clarke
authors.initials: MC
authors.lastname: Miller
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, 800 Rose St. MS-415 Medical Center, Lexington, KY 40536-0298, USA.
authors.forename: Jacqueline D
authors.initials: JD
authors.lastname: Fetherston
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, 800 Rose St. MS-415 Medical Center, Lexington, KY 40536-0298, USA.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Pickett
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, 800 Rose St. MS-415 Medical Center, Lexington, KY 40536-0298, USA.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Bobrov
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, 800 Rose St. MS-415 Medical Center, Lexington, KY 40536-0298, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Weaver
authors.affiliation: Department of Biology, 101 T. H. Morgan Building, Lexington, KY 40506-0225, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: DeMoll
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, 800 Rose St. MS-415 Medical Center, Lexington, KY 40536-0298, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Perry
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D010636:Phenols / Q000378:metabolism*; D017262:Siderophores / Q000096:biosynthesis*; D013844:Thiazoles / Q000378:metabolism*; D015533:Transcriptional Activation; D015010:Yersinia pestis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D010636:Phenols; D017262:Siderophores; D013844:Thiazoles; C104398:yersiniabactin