The Hybrid Antibiotic Thiomarinol A Overcomes Intrinsic Resistance in <i>Escherichia coli</i> Using a Privileged Dithiolopyrrolone Moiety.

ABSTRACT: An impermeable outer membrane and multidrug efflux pumps work in concert to provide Gram-negative bacteria with intrinsic resistance against many antibiotics. These resistance mechanisms reduce the intracellular concentrations of antibiotics and render them ineffective. The natural product thiomarinol A combines holothin, a dithiolopyrrolone antibiotic, with marinolic acid A, a close analogue of mupirocin. The hybridity of thiomarinol A converts the mupirocin scaffold from inhibiting Gram-positive bacteria to inhibiting both Gram-positive and -negative bacteria. We found that thiomarinol A accumulates significantly more than mupirocin within the Gram-negative bacterium Escherichia coli, likely contributing to its broad-spectrum activity. Antibiotic susceptibility testing of E. co

SUBMITTER: Johnson RM 

PROVIDER: S-EPMC11235417 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature