ArticleScientific reports2015
In vitro and in vivo Evaluation of Synergism between Anti-Tubercular Spectinamides and Non-Classical Tuberculosis Antibiotics.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 60 citations in OpenAlex.
- Integrated computational and experimental approaches for drug repurposing targeting key Mycobacterium tuberculosis proteins.Molecular diversity · 2026Article
- Netupitant Exhibits Potent Activity onACS infectious diseases · 2025Article
- Strategic re-engineering of antibiotics.Nature reviews bioengineering · 2025Article
- Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- A modified BPaL regimen for tuberculosis treatment replaces linezolid with inhaled spectinamides.eLife · 2024Article
- Identification of gene targets that potentiate the action of rifampicin onMicrobiology (Reading, England) · 2024Article
- Development of 2nd generation aminomethyl spectinomycins that overcome native efflux inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Developing synergistic drug combinations to restore antibiotic sensitivity in drug-resistantAntimicrobial agents and chemotherapy · 2023Article
- Characterization of spectinamide 1599 efficacy against different mycobacterial phenotypes.Tuberculosis (Edinburgh, Scotland) · 2023Article
- Mab2780c, a TetV-like efflux pump, confers high-level spectinomycin resistance in mycobacterium abscessus.Tuberculosis (Edinburgh, Scotland) · 2023Article
- Drug Repurposing Approaches towards Defeating Multidrug-Resistant Gram-Negative Pathogens: Novel Polymyxin/Non-Antibiotic Combinations.Pathogens (Basel, Switzerland) · 2022Review
- "Upcycling" known molecules and targets for drug-resistant TB.Frontiers in cellular and infection microbiology · 2022Article
- Preclinical Evaluation of Inhalational Spectinamide-1599 Therapy against Tuberculosis.ACS infectious diseases · 2021Article
- Replacement of S14 Protein in Ribosomes of Zinc-Starved Mycobacteria Reduces Spectinamide Sensitivity.Antimicrobial agents and chemotherapy · 2021Article
- Development of a novel secondary phenotypic screen to identify hits within the mycobacterial protein synthesis pipeline.FASEB bioAdvances · 2020Article
- Molecule Property Analyses of Active Compounds forJournal of medicinal chemistry · 2020Review
- Potential anti-TB investigational compounds and drugs with repurposing potential in TB therapy: a conspectus.Applied microbiology and biotechnology · 2020Review
- Sugar-Pirating as an Enabling Platform for the Synthesis of 4,6-Dideoxyhexoses.Journal of the American Chemical Society · 2020Article
- Mycobacterium culturing and drug resistance of osteoarticular tuberculosis in Xinjiang, China.Medicine · 2020Article
- Aminomethyl spectinomycins: a novel antibacterial chemotype for biothreat pathogens.The Journal of antibiotics · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Spectinamides are new semi-synthetic spectinomycin derivatives with potent anti-tubercular activity. The reported synergism of the precursor spectinomycin with other antibiotics prompted us to examine whether spectinamides sensitize M. tuberculosis to other antibiotics not traditionally used in the treatment of tuberculosis to potentially expand therapeutic options for MDR/XDR Tuberculosis. Whole cell synergy checkerboard screens were performed using the laboratory strain M. tuberculosis H37Rv, lead spectinamide 1599, and a broad panel of 27 antibiotics. In vitro, 1599 synergized with 11 drugs from 6 antibiotic classes. The observed synergy was tested against clinical isolates confirming synergy with Clarithromycin, Doxycycline and Clindamycin, combinations of which were taken forward for in vivo efficacy determination. Co-administration of 1599 and clarithromycin provided additional bacterial killing in a mouse model of acute tuberculosis infection, but not in a chronic infection model. Further studies indicated that mismatched drug exposure profiles likely permitted induction of phenotypic clarithromycin resistance and subsequent loss of synergism. These studies highlight the importance of validating in vitro synergism and the challenge of matching drug exposures to obtain a synergistic outcome in vivo. Results from this study indicate that a 1599 clarithromycin combination is potentially viable, providing the drug exposures can be carefully monitored.
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