Re-sensitization of Multidrug-Resistant and Colistin-Resistant Gram-Negative Bacteria to Colistin by Povarov/Doebner-Derived Compounds.

ABSTRACT: Colistin, typically viewed as the antibiotic of last resort to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, had fallen out of favor due to toxicity issues. The recent increase in clinical usage of colistin has resulted in colistin-resistant isolates becoming more common. To counter this threat, we have investigated previously reported compounds, HSD07 and HSD17, and developed 13 compounds with more desirable drug-like properties for colistin sensitization against 16 colistin-resistant bacterial strains, three of which harbor the plasmid-borne mobile colistin resistance (mcr-1). Lead compound HSD1624, which has a lower LogD_pH7.4 (2.46) compared to HSD07 (>5.58), reduces the minimum inhibitory concentration (MIC) o

SUBMITTER: Onyedibe KI 

PROVIDER: S-EPMC10547215 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature