The phytotoxin albicidin is a novel inhibitor of DNA gyrase

Hashimi, SM, Wall, M. K., Smith, A. B., Maxwell, A. and Birch, R. G. (2007) The phytotoxin albicidin is a novel inhibitor of DNA gyrase. Antimicrobial Agents and Chemotherapy, 51 1: 181-187. doi:10.1128/AAC.00918-06

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Author Hashimi, SM
Wall, M. K.
Smith, A. B.
Maxwell, A.
Birch, R. G.
Title The phytotoxin albicidin is a novel inhibitor of DNA gyrase
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
Publication date 2007
Sub-type Article (original research)
DOI 10.1128/AAC.00918-06
Open Access Status File (Publisher version)
Volume 51
Issue 1
Start page 181
End page 187
Total pages 7
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2008
Language eng
Subject C1
270400 Botany
620000 - Plant Production and Plant Primary Products
Abstract Xanthomonas albilineans produces a family of polyketide-peptide compounds called albicidins which are highly potent antibiotics and phytotoxins as a result of their inhibition of prokaryotic DNA replication. Here we show that albicidin is a potent inhibitor of the supercoiling activity of bacterial and plant DNA gyrases, with 50% inhibitory concentrations (40 to 50 nM) less than those of most coumarins and quinolones. Albicidin blocks the religation of the cleaved DNA intermediate during the gyrase catalytic sequence and also inhibits the relaxation of supercoiled DNA by gyrase and topoisomerase W. Unlike the coumarins, albicidin does not inhibit the ATPase activity of gyrase. In contrast to the quinolones, the albicidin concentration required to stabilize the gyrase cleavage complex increases 100-fold in the absence of ATP. The slow peptide poisons microcin B17 and CcdB also access ATP-dependent conformations of gyrase to block religation, but in contrast to albicidin, they do not inhibit supercoiling under routine assay conditions. Some mutations in gyrA, known to confer high-level resistance to quinolones or CcdB, confer low-level resistance or hypersensitivity to albicidin in Escherichia coli. Within the albicidin biosynthesis region in X. albilineans is a gene encoding a pentapeptide repeat protein designated AlbG that binds to E. coli DNA gyrase and that confers a sixfold increase in the level of resistance to albicidin in vitro and in vivo. These results demonstrate that DNA gyrase is the molecular target of albicidin and that X. albilineans encodes a gyrase-interacting protein for self-protection. The novel features of the gyrase-albicidin interaction indicate the potential for the development of new antibacterial drugs.
Keyword Microbiology
Pharmacology & Pharmacy
Leaf Scald Disease
Xanthomonas-albilineans
Escherichia-coli
Strand-passage
Quinolone Resistance
Bacterial Toxin
Molecular-basis
Binding-site
Microcin B17
Gene
Q-Index Code C1

 
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Created: Mon, 18 Feb 2008, 15:59:07 EST