Antibiotic drugs targeting bacterial RNAs

Hong, Wang; Zeng, Jie; Xie, Jianping

doi:10.1016/j.apsb.2014.06.012

Cited by 91 publications

(51 citation statements)

References 104 publications

(106 reference statements)

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“…We found this to be the case when testing the effects of queueing on the survival of cells treated with chloramphenicol. Chloramphenicol is an antibiotic that inhibits protein translation by binding to bacterial ribosomes and inhibiting protein synthesis, thereby inhibiting bacterial growth 42 . Induction of CFP-LAA does not increase survival of antibiotic treatment when treated with chloramphenicol alone (Fig.…”

Section: Chloramphenicol Inhibits the Synthetic Queuementioning

confidence: 99%

Proteolytic queues at ClpXP increase antibiotic tolerance

Deter

Abualrahi

Jadhav

et al. 2019

Preprint

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Antibiotic tolerance is a widespread phenomenon that renders antibiotic treatments less effective and facilitates antibiotic resistance. Here we explore the role of proteases in antibiotic tolerance, short-term population survival of antibiotics, using queueing theory (i.e. the study of waiting lines), computational models, and a synthetic biology approach. Proteases are key cellular components that degrade proteins and play an important role in a multi-drug tolerant subpopulation of cells, called persisters. We found that queueing at the protease ClpXP increases antibiotic tolerance ~80 and ~60 fold in an E. coli population treated with ampicillin and ciprofloxacin, respectively. There does not appear to be an effect on antibiotic persistence, which we distinguish from tolerance based on population decay. These results demonstrate that proteolytic queueing is a practical method to probe bacterial tolerance and related genes, while limiting the unintended consequences frequently caused by gene knockout and overexpression.

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Section: Chloramphenicol Inhibits the Synthetic Queuementioning

confidence: 99%

Proteolytic queues at ClpXP increase antibiotic tolerance

Deter

Abualrahi

Jadhav

et al. 2019

Preprint

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“…Minocycline is an FDA-approved, second-generation tetracycline class antibiotic with an established safety pro le that has been used in clinic for more than 30 years. Minocycline binds to the bacterial 30S ribosomal subunit, inhibiting the binding of RNA to ribosomes, and interferes with protein synthesis [51].…”

Section: Biological Activities Of Minocyclinementioning

confidence: 99%

Minocycline Might Be an Adjunctive Therapy Option for the Treatment of COVID-19: In Silico Screening, Structure-affinity Relationship, and Literature Review

Xiao¹

2020

Preprint

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Abstract Up to now, there is no specific therapy for the globally ongoing COVID-19. To explore potential inhibitors of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) for the treatment of novel coronavirus disease (COVID-19), in silico screening of 135 clinical drugs was performed targeting on 3-chymotrypsin-like protease (3CLpro, or M pro ). Six drugs including anti-HIV drug (raltegravir), antibacterial drugs (cefonicid, cefoperazone, minocycline), and antidiabetic drugs (canaglifozin, glyburide) showed high binding affinities (≤ -8.5 kcal/mol) and interesting binding conformations compared with the designed co-crystal ligand N3 (-7.7 kcal/mol). In which the antibiotic minocycline, an inhibitor of bacterial ribosomal rRNA, showed the highest binding affinity (-9.6 kcal/mol). Valuable hydrogen bonding and hydrophobic interactions were found between minocycline and Mpro active site. Beside the hydrogen bond with Cys145, minocycline formed a Pi-Cation with His41, which strongly supported minocycline as a Michael Addition acceptor to bind with the catalytic site of Mpro . The structure-affinity relationship was studied based on molecular docking of minocycline analogues. Literature review found that minocycline had both in vitro and in vivo broad-spectrum antiviral as well as anti-inflammatory activities, and the levels of a broad-spectrum of biological markers during minocycline administration were opposed to those of COVID-19 condition (both severe and non-severe). Minocycline deserves in vitro and in vivo evaluations as SARS-CoV-2 inhibitor as well as a randomized controlled trial to investigate the efficacy for COVID-19. These studies will shed new light on an adjuvant treatment strategy for this potentially lethal viral disease.

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“…208 but their antibacterial activities were lower than, or in the same range as, 95. [209][210][211][212] Blasticidin S (96) is a nucleoside analogue consisting of a cytosine linked to a dideoxyhexose and bonded to a modified arginine (Figure 49). [213][214][215] This analogue In order to elucidate the substrate specificity of alanyl-tRNA synthetase, Ueda et al…”

Section: Ribosomal Peptidyl Center Inhibitorsmentioning

confidence: 99%

Nucleoside Derived Antibiotics to Fight Microbial Drug Resistance: New Utilities for an Established Class of Drugs?

2016

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Novel antibiotics are urgently needed to combat the rise of infections due to drug-resistant microorganisms. Numerous natural nucleosides and their synthetically modified analogues have been reported to have moderate to good antibiotic activity against different bacterial and fungal strains. Nucleoside-based compounds target several crucial processes of bacterial and fungal cells such as nucleoside metabolism and cell wall, nucleic acid, and protein biosynthesis. Nucleoside analogues have also been shown to target many other bacterial and fungal cellular processes although these are not well characterized and may therefore represent opportunities to discover new drugs with unique mechanisms of action. In this Perspective, we demonstrate that nucleoside analogues, cornerstones of anticancer and antiviral treatments, also have great potential to be repurposed as antibiotics so that an old drug can learn new tricks.

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Antibiotic drugs targeting bacterial RNAs

Cited by 91 publications

References 104 publications

Proteolytic queues at ClpXP increase antibiotic tolerance

Proteolytic queues at ClpXP increase antibiotic tolerance

Minocycline Might Be an Adjunctive Therapy Option for the Treatment of COVID-19: In Silico Screening, Structure-affinity Relationship, and Literature Review

Nucleoside Derived Antibiotics to Fight Microbial Drug Resistance: New Utilities for an Established Class of Drugs?

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