ArticleMicrobial cell factories2024
Repurposing harmaline as a novel approach to reverse tmexCD1-toprJ1-mediated tigecycline resistance against klebsiella pneumoniae infections.
Article in Microbial cell factories, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Repurposing loratadine to reverse colistin resistance inEmerging microbes & infections · 2026Article
- Sodium butyrate augments the antibacterial activity of tetracycline against clinical isolates of multidrug-resistant Vibrio cholerae.Gut pathogens · 2026Article
- Novel Antimicrobials from Computational Modelling and Drug Repositioning: PotentialMolecules (Basel, Switzerland) · 2025Review
- The potential application of isoxanthohumol in inhibiting Clostridium perfringens infection by targeting the type IV pili.Microbial cell factories · 2025Article
- Breaking the resistance: integrative approaches with novel therapeutics against Klebsiella pneumoniae.Archives of microbiology · 2024Review
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Authors and funding
8 authors.
Funding
Abstract
backgroundA novel plasmid-mediated resistance-nodulation-division (RND) efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae tremendously threatens the use of convenient therapeutic options in the post-antibiotic era, including the "last-resort" antibiotic tigecycline.
resultsIn this work, the natural alkaloid harmaline was found to potentiate tigecycline efficacy (4- to 32-fold) against tmexCD1-toprJ1-positive K. pneumoniae, which also thwarted the evolution of tigecycline resistance. Galleria mellonella and mouse infection models in vivo further revealed that harmaline is a promising candidate to reverse tigecycline resistance. Inspiringly, harmaline works synergistically with tigecycline by undermining tmexCD1-toprJ1-mediated multidrug resistance efflux pump function via interactions with TMexCD1-TOprJ1 active residues and dissipation of the proton motive force (PMF), and triggers a vicious cycle of disrupting cell membrane integrity and metabolic homeostasis imbalance.
conclusionThese results reveal the potential of harmaline as a novel tigecycline adjuvant to combat hypervirulent K. pneumoniae infections.
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