ent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitors.

ABSTRACT: Colistin is a last-resort antibiotic for the treatment of multidrug resistant Gram-negative bacterial infections. Recently, a natural ent-beyerene diterpene was identified as a promising inhibitor of the enzyme responsible for colistin resistance mediated by lipid A aminoarabinosylation in Gram-negative bacteria, namely, ArnT (undecaprenyl phosphate-alpha-4-amino-4-deoxy-l-arabinose arabinosyl transferase). Here, semisynthetic analogues of hit were designed, synthetized, and tested against colistin-resistant Pseudomonas aeruginosa strains including clinical isolates to exploit the versatility of the diterpene scaffold. Microbiological assays coupled with molecular modeling indicated that for a more efficient colistin adjuvant activity, likely resulting from inhibition of the

SUBMITTER: Quaglio D 

PROVIDER: S-EPMC8009527 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature