Alternative Sigma Factors and Their Roles in Bacterial Virulence

Abstract

SUMMARY Sigma factors provide promoter recognition specificity to RNA polymerase holoenzyme, contribute to DNA strand separation, and then dissociate from the core enzyme following transcription initiation. As the regulon of a single sigma factor can be composed of hundreds of genes, sigma factors can provide effective mechanisms for simultaneously regulating expression of large numbers of prokaryotic genes. One newly emerging field is identification of the specific roles of alternative sigma factors in regulating expression of virulence genes and virulence-associated genes in bacterial pathogens. Virulence genes encode proteins whose functions are essential for the bacterium to effectively establish an infection in a host organism. In contrast, virulence-associated genes can contribute to bacterial survival in the environment and therefore may enhance the capacity of the bacterium to spread to new individuals or to survive passage through a host organism. As alternative sigma factors have been shown to regulate expression of both virulence and virulence-associated genes, these proteins can contribute both directly and indirectly to bacterial virulence. Sigma factors are classified into two structurally unrelated families, the σ70 and the σ54 families. The σ70 family includes primary sigma factors (e.g., Bacillus subtilis σA) as well as related alternative sigma factors; σ54 forms a distinct subfamily of sigma factors referred to as σN in almost all species for which these proteins have been characterized to date. We present several examples of alternative sigma factors that have been shown to contribute to virulence in at least one organism. For each sigma factor, when applicable, examples are drawn from multiple species.

RelA regulates virulence and intracellular survival of Francisella novicida

“…It has been proposed that growth defects observed in relA mutants can be attributed to the lack of (p)ppGpp-dependent expression of the rpoS gene, which encodes s S (Gentry et al, 1993). This alternative sigma factor controls expression of genes or operons involved in protecting cells from stress, including stationary phase survival, high osmolarity, oxidative damage and acidic pH (Kazmierczak et al, 2005). It is thought that (p)ppGpp increases the ability of both s S and s 32 to compete with the vegetative sigma factor s 70 for RNA polymerase (Jishage et al, 2002), presumably resulting in increased expression of s S -induced general stress response and s 32 -dependent heat-shock response genes.…”

The cyclic AMP receptor protein modulates quorum sensing, motility and multiple genes that affect intestinal colonization in Vibrio cholerae

“…Conserved functions of s E in Gram-negative bacteria include the synthesis, assembly and homeostasis of lipopolysaccharide and outer-membrane porins (Rhodius et al, 2006). s E has been shown to contribute to virulence in several pathogenic bacteria, including Salmonella, Haemophilus and V. cholerae (Kazmierczak et al, 2005;Kovacikova & Skorupski 2002a). Furthermore, expression of fumarate reductase subunits frdABCD was significantly diminished in the Dcrp mutant.…”

Quantitative proteomics of intracellular Porphyromonas gingivalis

“…A physiological theme for sigma-54-dependent genes has yet to emerge, as the target genes participate in a wide range of processes. However, in plant pathogens, sigma-54 controls type III secretion [59], a major pathway for delivery of bioactive bacterial proteins into host cells that contributes to bacterial invasion and survival. Over-expression of a TetR family transcriptional regulator was also observed.…”