title: Bacterial Transcription as a Target for Antibacterial Drug Development.
abstract: Transcription, the first step of gene expression, is carried out by the enzyme RNA polymerase (RNAP) and is regulated through interaction with a series of protein transcription factors. RNAP and its associated transcription factors are highly conserved across the bacterial domain and represent excellent targets for broad-spectrum antibacterial agent discovery. Despite the numerous antibiotics on the market, there are only two series currently approved that target transcription. The determination of the three-dimensional structures of RNAP and transcription complexes at high resolution over the last 15 years has led to renewed interest in targeting this essential process for antibiotic development by utilizing rational structure-based approaches. In this review, we describe the inhibition of the bacterial transcription process with respect to structural studies of RNAP, highlight recent progress toward the discovery of novel transcription inhibitors, and suggest additional potential antibacterial targets for rational drug design.
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Cong
authors.initials: C
authors.lastname: Ma
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia Peter.Lewis@newcastle.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lewis
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D000077732:Fidaxomicin; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D012294:Rifamycins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D013045:Species Specificity; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010456:Peptides, Cyclic; D012294:Rifamycins; D014157:Transcription Factors; D012321:DNA-Directed RNA Polymerases; D000077732:Fidaxomicin