Alternative respiratory electron transport pathways drive differential aminoglycoside susceptibility

The bacterial electron transport system (ETS) is a highly branched and modular network that interfaces directly with the proton motive force (PMF) to drive ATP synthesis, solute transport, and cellular homeostasis (1–5). Distinct ETS branches differ in their capacities for proton translocation, redox balancing, and membrane polarization. The rewiring of cellular energetics has emerged as a recurrent strategy through which bacteria attenuate drug efficacy by shifting metabolic states, reducing membrane potential, and suppressing reactive oxygen species-linked killing mechanisms (6, 7). Here, we probe the interplay between respiratory routes and antibiotic susceptibilities.