Fig. 7.

Proposed relationships of PTS, cAMP-Crp, respiration, ROS accumulation, and damage repair in stress-mediated bacterial death. Bactericidal treatments produce primary lesions (a) that are recognized by repair systems (b). If repair is sufficient, cells survive (c) unless overwhelmed by downstream damage. Repair increases demand for ATP and stimulates respiration (d), resulting in elevated ATP synthesis. ROS accumulate as by-products during ATP synthesis (e); ROS damage macromolecules (f), including DNA, protein, and lipids. Macromolecular damage from ROS stimulates additional ROS accumulation and damage in a self-amplifying cycle (f and g) that leads to cellular repair being overwhelmed and ultimately to cell death unless ROS-detoxifying systems are sufficient to suppress ROS accumulation (h). The demand for ATP by repair also stimulates carbohydrate metabolism via the PTS (i), which in turn stimulates adenyl cyclase (j) to synthesize cAMP (k). cAMP binds to and activates Crp (l), which up-regulates genes involved in the TCA cycle (m), thereby producing elevated levels of NADH that fuel respiration (n), subsequent ATP synthesis, and ROS production. L-shaped green shading indicates pathways from which pan-tolerance mutants may emerge.