by Blasco B; Jang S; Terauchi H; Kobayashi N; Suzuki S; Akao Y; Ochida A; Morishita N; Takagi T; Nagamiya H; Suzuki Y; Watanabe T; Lee H; Lee S; David Shum D; Cho A; Koh D; Park S; Lee H; Kim K; Ropponen HK; Augusto da Costa RM; Dunn S; Ghosh S; Sjö P; Piddock LJV. eBioMedicine 2024. 102: 105073 doi: 10.1016/j.ebiom.2024.105073
Summary: The World Health Organization has identified the threat posed by drug-resistant gram-negative bacteria as a global health priority. However, the current pipeline for new antibiotics is inadequate; antibacterials with novel mechanisms of action are urgently needed. The authors of this manuscript aimed to identify new chemical entities with activity against multidrug-resistant strains of priority pathogens Klebsiella pneumoniae and Acinetobacter baumannii. They implemented and validated a primary whole cell screening methodology to test new chemical matter from the proprietary compound collections of three pharmaceutical companies. Two new scaffolds with activity against multidrug-resistant A. baumannii were identified. This study provides evidence that a screening strategy starting with multidrug-resistant bacteria can be useful for screening new chemical matter.
