Combating multidrug-resistance in S. pneumoniae: a G-quadruplex binding inhibitor of efflux pump and its bio-orthogonal assembly.

ABSTRACT: Antibiotic resistance poses a significant global health threat, necessitating innovative strategies to combat multidrug-resistant bacterial infections. Streptococcus pneumoniae, a pathogen responsible for various infections, harbors highly conserved DNA quadruplexes in genes linked to its pathogenesis. In this study, we introduce a novel approach to counter antibiotic resistance by stabilizing G-quadruplex structures within the open reading frames of key resistance-associated genes (pmrA, recD and hsdS). We synthesized An4, a bis-anthracene derivative, using Cu(I)-catalyzed azide-alkyne cycloaddition, which exhibited remarkable binding and stabilization of the G-quadruplex in the pmrA gene responsible for drug efflux. An4 effectively permeat

SUBMITTER: Chaudhuri R 

PROVIDER: S-EPMC11059089 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature