FIG 8.

Proposed model of peptidoglycan-targeting antibiotic- and DFP-mediated toxicity to bacterial cells. DFP chelates ferric iron in the medium (DFP-Fe³⁺). When antibiotics are present, they destabilize the cellular membrane(s), allowing DFP-Fe³⁺ to readily enter the cell. DFP-Fe³⁺ then is reduced to Fe²⁺ in the highly reducing environment of the bacterial cytoplasm. Reduced DFP-Fe²⁺ is a known radical generator in the presence of O₂ or H₂O₂ and leads to the production of ROS. DFP also contributes to a state of iron starvation (by shielding iron from binding to Fur), perhaps leading to excessive iron uptake, which contributes further to the generation of ROS. The supraphysiologic level of ROS generated under these conditions leads to cell death and/or inhibition of growth.