Alternative sigma factor interactions in Salmonella: σE and σH promote antioxidant defences by enhancing σS levels



Hierarchical interactions between alternative sigma factors control sequential gene expression in Gram-positive bacteria, whereas alternative sigma factors in Gram-negative bacteria are generally regarded to direct expression of discrete gene subsets. In Salmonella enterica serovar Typhimurium (S. Typhimurium), σE responds to extracytoplasmic stress, whereas σH responds to heat shock and σS is induced during nutrient limitation. Deficiency of σE, σH or σS increases S. Typhimurium susceptibility to oxidative stress, but an analysis of double and triple mutants suggested that antioxidant actions of σE and σH might be dependent on σS. Transcriptional profiling of mutant Salmonella lacking σE revealed reduced expression of genes dependent on σH and σS in addition to σE. Further investigation demonstrated that σE augments σS levels during stationary phase via enhanced expression of σH and the RNA-binding protein Hfq, leading to increased expression of σS-dependent genes and enhanced resistance to oxidative stress. Maximal expression of the σS-regulated gene katE required σE in Salmonella-infected macrophages as well as stationary-phase cultures. Interactions between alternative sigma factors permit the integration of diverse stress signals to produce coordinated genetic responses.