Figure 1. Drug-target interactions and associated cell death mechanisms.

a) Quinolone antibiotics interfere with changes in DNA supercoiling by binding to topoisomerase II or IV. This leads to the formation of double-stranded DNA breaks and cell death in either a protein synthesis dependent or protein synthesis independent fashion. b) β-lactams inhibit transpeptidation by binding to PBPs on maturing peptidoglycan strands. The decrease in peptidoglycan synthesis and increase in autolysins leads to lysis and cell death. c) Aminoglycosides bind to the 30S subunit of the ribosome and cause misincorporation of amino acids into elongating peptides. These mistranslated proteins can misfold, and incorporation of misfolded membrane proteins into the cell envelope leads to increased drug uptake, which together with an increase in ribosome binding has been associated with cell death.