Aminoglycoside uptake, stress, and potentiation in Gram-negative bacteria: new therapies with old molecules

Abstract

SUMMARY Aminoglycosides (AGs) are long-known molecules successfully used against Gram-negative pathogens. While their use declined with the discovery of new antibiotics, they are now classified as critically important molecules because of their effectiveness against multidrug-resistant bacteria. While they can efficiently cross the Gram-negative envelope, the mechanism of AG entry is still incompletely understood, although this comprehension is essential for the development of new therapies in the face of the alarming increase in antibiotic resistance. Increasing antibiotic uptake in bacteria is one strategy to enhance effective treatments. This review aims, first, to consolidate old and recent knowledge about AG uptake; second, to explore the connection between AG-dependent bacterial stress and drug uptake; and finally, to present new strategies of potentiation of AG uptake for more efficient antibiotic therapies. In particular, we emphasize on the connection between sugar transport and AG potentiation.

Molecular determinant deciphering of MIC-guided RND efflux substrates in E. coli

“…Frontiers in Drug Discovery frontiersin.org enzymatic transformation phenomena and 30S ribosome subunit mutation (McDermott et al, 2003;Ojdana et al, 2017). Gentamicin, tobramycin and amikacin are the most widely used aminoglycosides with minimal resistance in clinical practice due to their accurate activity against Gram-negative aerobic strains (Lang et al, 2023). Efflux phenomena also occur in resistance.…”