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Title: ALTERNATIVE SIGMA FACTOR INTERACTIONS IN SALMONELLA: SIGMA E AND SIGMA H PROMOTE ANTIOXIDANT DEFENCES BY ENHANCING SIGMA S LEVELS

Author
item BANG, LEL-SOO - UNIVERISTY OF WASHINGTON
item Frye, Jonathan
item MCCLELLAND, MICHAEL - SIDNEY KIMMEL CANCER CTR
item VELAYUDHAN, JOYTI - UNIVERSITY OF WASHINGTON
item FANG, FERRIC - UNIVERSITY OF WASHINGTON

Submitted to: Molecular Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/13/2005
Publication Date: 5/1/2005
Citation: Bang, L., Frye, J.G., Mcclelland, M., Velayudhan, J., Fang, F.C. 2005. Alternative sigma factor interactions in salmonella: sigma e and sigma h promote antioxidant defences by enhancing sigma s levels. Molecular Microbiology. 56(3):811-823.

Interpretive Summary: Sigma factors are responsible for regulating gene expression in bacteria at a global level. Salmonella has six sigma factors that control diverse functions such as general gene expression (sigma70), motility (sigmaF), stationary/stress phase (sigmaS), membrane stress (sigmaE), heat shock (sigmaH) and nitrogen metabolism (sigmaN). These global regulators must interact to fine tune gene expression patterns during complex events like the infection process. To identify some of these interactions, gene expression of Salmonella strains lacking sigmaE, sigmaH and sigmaS were determined by DNA microarray. Analysis of this data revealed that sigmaE and sigmaH enhance sigmaS controlled expression of the Salmonella antioxidant defense and all three sigma factors are required for a successful infection. These findings expand our knowledge of how bacteria regulate gene expression at the global level, and have a broad impact on researchers investigating global and virulence gene regulation in pathogenic bacteria like Salmonella.

Technical Abstract: 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, sigmaE responds to extracytoplasmic stress, whereas sigmaH responds to heat shock and sigmaS is induced during nutrient limitation. Deficiency of sigmaE, sigmaH or sigmaS increases S. Typhimurium susceptibility to oxidative stress, but an analysis of double and triple mutants suggested that antioxidant actions of sigmaE and sigmaH might be dependent on sigmaS. Transcriptional profiling of mutant Salmonella lacking sigmaE revealed reduced expression of genes dependent on sigmaH and sigmaS in addition to sigmaE. Further investigation demonstrated that sigmaE augments sigmaS levels during stationary phase via enhanced expression of sigmaH and the RNA-binding protein Hfq, leading to increased expression of sigmaS-dependent genes and enhanced resistance to oxidative stress. Maximal expression of the sigmaS-regulated gene katE required sigmaE 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.