Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action

The Journal of Antibiotics
Chinwe U Chukwudi, Liam Good

Abstract

The 16S rRNA binding mechanism proposed for the antibacterial action of the tetracyclines does not explain their mechanism of action against non-bacterial pathogens. In addition, several contradictory base pairs have been proposed as their binding sites on the 16S rRNA. This study investigated the binding of minocycline and doxycycline to short double-stranded RNAs (dsRNAs) of random base sequences. These tetracyclines caused a dose-dependent decrease in the fluorescence intensities of 6-carboxyfluorescein (FAM)-labelled dsRNA and ethidium bromide (EtBr)-stained dsRNA, indicating that both drugs bind to dsRNA of random base sequence in a manner that is competitive with the binding of EtBr and other nucleic acid ligands often used as stains. This effect was observable in the presence of Mg(2+). The binding of the tetracyclines to dsRNA changed features of the fluorescence emission spectra of the drugs and the CD spectra of the RNA, and inhibited RNase III cleavage of the dsRNA. These results indicate that the double-stranded structures of RNAs may have a more important role in their interaction with the tetracyclines than the specific base pairs, which had hitherto been the subject of much investigation. Given the diverse functi...Continue Reading

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Citations

Jun 2, 2016·Antimicrobial Agents and Chemotherapy·Chinwe U Chukwudi
Jul 7, 2020·PloS One·Chinwe Uzoma Chukwudi, Liam Good
Nov 2, 2017·The Journal of Antimicrobial Chemotherapy·Hélène ScornecChristophe Merlin
Feb 10, 2019·The Journal of Antibiotics·Chinwe U Chukwudi, Liam Good
Dec 24, 2020·Expert Review of Anti-infective Therapy·Md Jamal Hossain, S M Abdur Rahman
Nov 23, 2021·Frontiers in Physiology·Hyun Jun JungPaul A Welling

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