<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Influence of antimicrobial compounds and the RNA-binding protein RibR on the activity of B vitamin-responsive bacterial riboswitches"^^ . "Riboswitches are RNA elements that modulate the expression of genes involved in essential\r\nmetabolic pathways and occur mainly in the bacterial world. Binding of a specific small ligand\r\nto the aptamer domain of the riboswitch typically results in repression of the downstream\r\ngenes, either by transcriptional termination or inhibition of translation. As riboswitches\r\nconstitute widespread genetic control elements, they are auspicious novel targets for antibiotic\r\nsubstances. The fact that hardly any new, effective antibiotic groups have been discovered in\r\nrecent decades poses a significant problem, especially regarding the spread of multi-resistant\r\npathogens, such as those from the so called ESKAPE group (Enterococcus faecium,\r\nStaphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas\r\naeruginosa and Enterobacter species).\r\nIn the first part of this study, thiamine pyrophosphate (TPP) riboswitches from relevant\r\npathogenic strains were identified using a newly adapted dual-luciferase reporter gene assay.\r\nTPP riboswitches from the ESKAPE pathogens Enterobacter spp., A. baumannii, P.\r\naeruginosa, K. pneumoniae and E. faecium as well as from the pathogens Streptococcus\r\npneumoniae and Mammaliicoccus sciuri were experimentally validated. The experimental\r\noutcome shows that the functionality of some of these riboswitches is dependent on the\r\nupstream promoter region. In addition to the affirmation of their function as regulators of gene\r\nexpression, the riboswitches were characterized by their mode of action using translational\r\nand transcriptional reporter gene fusions. The thiE TPP riboswitch from M. sciuri and the\r\nthiBPQ riboswitch from Enterobacter spp. exhibit translational regulation, while the thiC\r\nriboswitches from P. aeruginosa and Enterobacter spp. mainly operate via termination of\r\ntranscription. For the thiC riboswitches from A. baumannii, E. faecium and K. pneumoniae a\r\ncombined function of translation inhibition and transcriptional termination was found.\r\nInterestingly, none of the riboswitches examined in this study were affected by the antibiotic\r\npyrithiamine, which is known to block the E. coli thiC riboswitch. The study of the\r\nK. pneumoniae thiC riboswitch identified several key nucleotides in the extended P3 stem\r\nregion of the aptamer that are responsible for the non-responsiveness of the riboswitch to\r\npyrithiamine pyrophosphate.\r\nThe second chapter of this study addresses the riboswitch-binding protein RibR. This protein\r\nwas first described in Bacillus subtilis as a regulatory element of flavin mononucleotide (FMN)\r\nriboswitches and has two different functional parts. While the N-terminal part has flavokinase\r\nactivity, the RNA-binding activity could be assigned to the C-terminal part of the protein.\r\nExpression of ribR in B. subtilis is induced by the presence of the sulfur sources methionine\r\nand taurine. The RibR protein of B. subtilis (RibRsub) counteracts the effect of the ligand FMN on FMN riboswitch activity, allowing expression of the downstream genes involved in riboflavin\r\nbiosynthesis even in the presence of high FMN levels.\r\nIn Bacillus amyloliquefaciens, a truncated RibR-variant (RibRamy) has been identified, which\r\nonly consists of a putative RNA-binding domain. Electrophoretic mobility shift assays showed\r\nthat RibRamy, just like RibRsub, binds both ribD FMN riboswitch aptamers from B. subtilis and\r\nB. amyloliquefaciens. CRISPR-Cas9 genome editing was used to generate B. subtilis ribR\r\nmutants expressing different versions of ribRsub and ribRamy. Enzyme assays with cell-free\r\nextracts from these strains which allowed monitoring of the FMN riboswitch activity confirmed\r\nthat RibRamy derepressed the FMN riboswitch even in the presence of FMN. This effect\r\ndepends on two conserved arginine residues in the primary structures of the B. subtilis and\r\nB. amyloliquefaciens RibR proteins as shown by site directed mutagenesis experiments.\r\nFurther results suggest a link between RibRamy and the response to oxidative stress in\r\nB. amyloliquefaciens."^^ . "2024" . . . . . . . "Anna"^^ . "Hübenthal"^^ . "Anna Hübenthal"^^ . . . . . . "Influence of antimicrobial compounds and the RNA-binding protein RibR on the activity of B vitamin-responsive bacterial riboswitches (PDF)"^^ . . . "PhD_thesis_final.pdf"^^ . . . "Influence of antimicrobial compounds and the RNA-binding protein RibR on the activity of B vitamin-responsive bacterial riboswitches (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Influence of antimicrobial compounds and the RNA-binding protein RibR on the activity of B vitamin-responsive bacterial riboswitches (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Influence of antimicrobial compounds and the RNA-binding protein RibR on the activity of B vitamin-responsive bacterial riboswitches (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Influence of antimicrobial compounds and the RNA-binding protein RibR on the activity of B vitamin-responsive bacterial riboswitches (Other)"^^ . . . . . . "small.jpg"^^ . . . "Influence of antimicrobial compounds and the RNA-binding protein RibR on the activity of B vitamin-responsive bacterial riboswitches (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #34817 \n\nInfluence of antimicrobial compounds and the RNA-binding protein RibR on the activity of B vitamin-responsive bacterial riboswitches\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .