Alternative respiratory electron transport pathways drive differential aminoglycoside susceptibility

Abstract

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.