Jing Lu, Mohammad A K Azad, Julie L M Moreau, Yan Zhu, Xukai Jiang, Mary Tonta, Rachel Lam, Hasini Wickremasinghe, Jinxin Zhao, Jiping Wang, Harold A Coleman, Luke E Formosa, Tony Velkov, Helena C Parkington, Alexander N Combes, Joseph Rosenbluh, Jian Li
Polymyxin antibiotics are often used as a last-line defense to treat life-threatening Gram-negative pathogens. However, polymyxin-induced kidney toxicity is a dose-limiting factor of paramount importance and can lead to suboptimal treatment. To elucidate the mechanism and develop effective strategies to overcome polymyxin toxicity, we employed a whole-genome CRISPR screen in human kidney tubular HK-2 cells and identified 86 significant genes that upon knock-out rescued polymyxin-induced toxicity. Specifically, we discovered that knockout of the inwardly rectifying potassium channels Kir4...
May 15, 2022: Cellular and Molecular Life Sciences: CMLS