Identification and characterisation of G-quadruplex DNA-forming sequences in the Pseudomonas aeruginosa genome
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Author(s)
Type
Journal Article
Abstract
A number of Gram-negative bacteria such as Pseudomonas aeruginosa are becoming resistant to front-line antibiotics. Consequently, there is a pressing need to find alternative bio-molecular targets for the development of new drugs. Since non-canonical DNA structures such as guanine-quadruplexes (G4s) have been implicated in regulating transcription, we were interested in determining whether there are putative quadruplex-forming sequences (PQS) in the genome of Pseudomonas aeruginosa. Using bioinformatic tools, we screened 36 genes potentially relevant to drug resistance for the presence of PQS and 10 of these were selected for biophysical characterisation (i.e. circular dichroism and thermal difference UV/Vis spectroscopy). These studies showed that three of these G-rich sequences (linked to murE, ftsB and mexC genes) form stable guanine-quadruplexes which were studied by NMR spectroscopy; detailed analysis of one of the sequences (mexC) confirmed that it adopts a two-quartet antiparallel quadruplex structure in the presence of K+ ions. We also show by FRET melting assays that small molecules can stabilise these three new G4 DNA structures under physiological conditions. These initial results could be of future interest in the development of new antibiotics with alternative bio-molecular targets which in turn would help tackle antimicrobial resistance.
Date Issued
2023-01-01
Date Acceptance
2022-11-13
Citation
RSC Chemical Biology, 2023, 4, pp.94-100
ISSN
2633-0679
Publisher
Royal Society of Chemistry
Start Page
94
End Page
100
Journal / Book Title
RSC Chemical Biology
Volume
4
Copyright Statement
© 2023 The Author(s). Published by the Royal Society of Chemistry. This article is licensed under aCreative Commons Attribution 3.0 Unported Licence (https://creativecommons.org/licenses/by/3.0/)
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Publication Status
Published
Date Publish Online
2022-11-15