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TonB is a bacterial energy transduction protein essential for nutrient import in Gram-negative bacteria. It functions as part of the TonB–ExbB–ExbD molecular motor complex in the inner membrane, harnessing the proton motive force to physically transmit energy across the periplasmic space, enabling active transport by TonB-dependent outer membrane receptors. TonB is necessary for the uptake of iron complexes (siderophores), vitamin B12, and other scarce nutrients, thereby contributing critically to bacterial survival and virulence in nutrient-limited environments. The protein spans the periplasm, interacting with outer membrane transporters (which contain a conserved TonB box motif) and is required for these receptors to transition from a closed to an open transport-competent conformation. Structurally, TonB is characterized by a transmembrane domain, a proline-rich linker, and a C-terminal region that binds to TonB box-containing receptors. Deletion or inhibition of TonB dramatically reduces bacterial virulence and growth in iron-restricted environments, making it a validated antibacterial target, especially for developing “Trojan horse” antibiotic strategies that exploit bacterial nutrient uptake pathways[2][5][6][8].
Inhibition of energy transduction to outer membrane receptors; Blockade of nutrient transport (by mimetic or competitive inhibitors)
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