Figure 1.

Mechanism of aminoglycoside uptake by Gram-negative bacterial cells and inhibition of protein synthesis. (A) Positively charged aminoglycosides (AG) enter the cell via electrostatic binding to the negatively charged components of the outer membrane (OM) including phospholipids and LPS in Gram-negative bacteria or teichoic acid in Gram-positive bacteria. This binding allows access of the AG to the periplasmic space. (B) A small number of AGs cross the inner membrane (IM) using the proton motive force and into the cytoplasm in an energy-dependent manner. (C) In the cytoplasm, AGs bind the 16S rRNA of the 30S ribosomal subunit where they inhibit initiation of translation, block elongation of translation, and induce error-prone translation. Mistranslated proteins are hypothesized to cause damage to the IM, facilitating AG entry into the cytoplasm.