Benzydamine Reverses TMexCD-TOprJ-Mediated High-Level Tigecycline Resistance in Gram-Negative Bacteria.
TLDR
In this article, the combination of benzydamine and tigecycline killed all drug-resistant pathogens during 24 hours of incubation and suppressed the evolution of tmexCD1-toprJ1 resistance.Abstract:
Recently, a novel efflux pump gene cluster called tmexCD1-toprJ1 and its variants have been identified, which undermine the antibacterial activity of tigecycline, one of the last remaining options effective against multidrug-resistant (MDR) Gram-negative bacteria. Herein, we report the potent synergistic effect of the non-steroidal anti-inflammatory drug benzydamine in combination with tigecycline at sub-inhibitory concentrations against various temxCD-toprJ-positive Gram-negative pathogens. The combination of benzydamine and tigecycline killed all drug-resistant pathogens during 24 h of incubation. In addition, the evolution of tigecycline resistance was significantly suppressed in the presence of benzydamine. Studies on the mechanisms of synergism showed that benzydamine disrupted the bacterial proton motive force and the functionality of this kind of novel plasmid-encoded resistance-nodulation-division efflux pump, thereby promoting the intracellular accumulation of tigecycline. Most importantly, the combination therapy of benzydamine and tigecycline effectively improved the survival of Galleria mellonella larvae compared to tigecycline monotherapy. Our findings provide a promising drug combination therapeutic strategy for combating superbugs carrying the tmexCD-toprJ gene.read more
Citations
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Bismuth Drugs Reverse Tet(X)-Conferred Tigecycline Resistance in Gram-Negative Bacteria
TL;DR: Five bismuth drugs, especially bismUTH nitrate [Bi(NO3)3], commonly used in clinical treatment of stomach-associated diseases, effectively boost the antibacterial activity of tigecycline against tet(X)-positive bacteria by inhibiting the enzymatic activity of Tet(X) protein.
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A Novel Tigecycline Adjuvant ML-7 Reverses the Susceptibility of Tigecycline-Resistant Klebsiella pneumoniae
TL;DR: Wang et al. as discussed by the authors showed that ML-7 hydrochloride (ML-7) dramatically potentiated tigecycline activity and showed that the combination exhibited synergistic bactericidal activities for TIGECYCLINE-resistant isolates during 24 hours.
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Metformin Reverses tmexCD1-toprJ1- and tet(A)-Mediated High-Level Tigecycline Resistance in K. pneumoniae
TL;DR: The potent synergistic effect of the antidiabetic drug metformin in combination with TIG against tet(A) mutant and tmexCD1-toprJ1 positive K. pneumoniae was confirmed in vivo using a well-studied Galleria mellonella larvae model.
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Bacterial proton motive force as an unprecedented target to control antimicrobial resistance
TL;DR: The potential of bacterial proton motive force (PMF) as an antibacterial target remains largely unexplored as discussed by the authors , and the potential of PMF disruptors in preventing the transmission of antibiotic resistance genes remains unexplored.
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Daunorubicin resensitizes Gram-negative superbugs to the last-line antibiotics and prevents the transmission of antibiotic resistance
TL;DR: In this paper , a Food and Drug Administration (FDA)-approved drug daunorubicin (DNR) drastically potentiates the activity of last-resort antibiotics against MDR-GN pathogens and biofilm-producing bacteria.
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