Fig. 7.
Proposed model for regulation of phenazine tolerance in A. tumefaciens.
Phenazine tolerance is regulated in both a constitutive (ActR-mediated) and inducible (SoxR-mediated) manner. ActR promotes phenazine tolerance in part by upregulating expression of cytochrome o oxidase (Cyo) at the expense of cytochrome d oxidase (Cyd) during aerobic growth. Cyo is more efficient at powering ATP synthesis and thereby supports energy-dependent defense and repair mechanisms. Levels of Cyo and Cyd may also affect how readily phenazines “steal” electrons from the electron transport chain and generate toxic superoxide radicals. Phenazines can directly oxidize and thereby activate SoxR. Activation of the SoxR regulon is likely energy dependent due to massive upregulation of several proteins, including superoxide dismutase (Sod), at least five efflux pumps, redox-related proteins such as ferredoxin, and other proteins that are as yet uncharacterized. The SoxR-regulated Sod becomes more important in the absence of ActR. Phzox = oxidized phenazines, Phzred = reduced phenazines.