Gene Expression and Virulence in Legionella: the Flagellar Regulon

In this chapter, the authors aimed to characterize the cascade of flaA regulation to obtain more information about mechanisms of gene regulation and about virulence of Legionella pneumophila. To analyze the cascade of flagellar gene regulation, the authors identified, cloned and characterized the regulators which may be involved in flaA regulation. Specific mutants of the identified regulators were generated and analyzed for flagellar gene expression. The authors also showed, that the sigma-54 activator protein FleQ is the master regulator of the flagellar regulon. Recently, the ability to analyze flagellar gene expression by transcriptome analysis using wild-type L. pneumophila strain Paris and the isogenic fliA mutant strain was developed. The regulation of the flagellum is linked to the expression of the virulent phenotype of Legionella. Phenotypic characteristics which are associated with the virulence of L. pneumophila have the ability to lyse human erythrocytes, to infect host cells, and to replicate inside host cells. It was shown recently that mutations in Toll-like receptor 5, which mediates the flagellin-dependant recognition of bacteria by the innate immune system in humans, is associated with the incidence of L. pneumophila infection. These results together indicate that various phenotypes associated with the flagellar regulon are of importance for virulence of L. pneumophila, demonstrating the importance of research into the flagellar regulon.