Inosine reverses multidrug resistance in Gram-negative bacteria carrying mobilized RND-type efflux pump gene cluster <i>tmexCD-toprJ</i>.

ABSTRACT: Antimicrobial resistance is rapidly increasing worldwide, highlighting the urgent need for pharmaceutical and nonpharmaceutical interventions to tackle different-to-treat bacterial infections. Tigecycline, a semi-synthesis glycylcycline for parenteral administration, is widely recognized as one of the few effective therapies available against pan-drug resistant Gram-negative pathogens. Regrettably, the efficacy of multiple drugs, including tigecycline, is currently being undermined due to the emergence of a recently discovered mobilized resistance-nodulation-division-type efflux pump gene cluster tmexCD1-toprJ1. Herein, by employing untargeted metabolomic approaches, we reveal that the expression of tmexCD1-toprJ1 disrupts bacterial purine metabolism, with inosine being ident

SUBMITTER: Li F 

PROVIDER: S-EPMC11495011 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature