Protective role of the RpoE (σE) and Cpx envelope stress responses against gentamicin killing of nongrowing Escherichia coli incubated under aerobic, phosphate starvation conditions.

The viability of Escherichia coli starved of nitrogen (N) or phosphorus (P) decreased by up to seven orders of magnitude during prolonged incubation under aerobic conditions when exposed to high levels of the antibiotic gentamicin, whereas viability of cells starved of carbon (C) was barely affected. However, the initial rate of killing was lower for P-starved cells than for N-starved cells. The transient resistance of P-starved cells was partially dependent upon the expression of the phosphate (Pho) and Cpx responses. Constitutive activity of the Cpx and RpoE (σ(E)) envelope stress regulons increased the resistance of P- and N-starved cells. The level of expression of the RpoE regulon was fourfold higher in P-starved cells than in N-starved cell at the time gentamicin was added. Gentamicin killing of nongrowing cells may thus require ongoing aerobic glucose metabolism and faulty synthesis of structural membrane proteins. However, membrane protein damage induced by gentamicin can be eliminated or repaired by RpoE- and Cpx-dependent mechanisms pre-emptively induced in P-starved cells, which reveals a novel mechanism of resistance to gentamicin that is active in certain circumstances.