Research ArticleANTIBIOTIC RESISTANCE

Repurposing a neurodegenerative disease drug to treat Gram-negative antibiotic-resistant bacterial sepsis

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Science Translational Medicine  18 Nov 2020:
Vol. 12, Issue 570, eabb3791
DOI: 10.1126/scitranslmed.abb3791

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PBT2 pumps up polymyxins

Bacterial resistance to antibiotics is a growing worldwide problem, and Enterobacterales with resistance to the polymyxin class of antibiotics are a critical threat. De Oliveira et al. repurposed a hydroxyquinoline compound called PBT2, which has undergone phase 2 clinical trials for neurodegenerative diseases, to break polymyxin antibiotic resistance in four different Gram-negative pathogens, including Klebsiella pneumoniae and Pseudomonas aeruginosa. In vitro, treatment with PBT2 disrupted the abundance of zinc and iron in the resistant bacteria, whereas in immunocompetent septic mice, PBT2 combined with polymyxins resulted in improved survival with reduced bacterial dissemination. These findings, while exciting, are still to be confirmed in humans.

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