Role of Flagella in Mucosal Colonization

Abstract

In recent years, different studies of bacterial flagella have unmasked novel features regarding their complex and sophisticated structure as well as their biological relevance beyond motility. This chapter focuses on these new structural and functional features of flagella, with emphasis on their ability to favor adherence, colonization, penetration, and translocation by bacterial pathogens and the resulting activation of innate immunity. For most bacterial pathogens, flagella and flagellum-driven motility are recognized as essential elements in their virulence scheme. Klose and Mekalanos constructed an rpoN (encoding s54)-null mutant of Vibrio cholerae and found that this strain was defective in motility, flagellation, and colonization in the infant-mouse colonization assay. In this study, they also identified three flagellar regulatory genes (flrABC), among which flrA and flrC encode σ54-activators; mutations in these two genes yielded mutants defective in colonization. Flagella purified from enterohemorrhagic Escherichia coli (EHEC) and E. coli K-12 showed similar levels of interleukin-8 (IL-8) induction as those for H6 flagella, suggesting that this is a property of flagella of some pathogenic bacteria as well as some members of the normal flora. It is possible that the conserved regions play an important role in generating an optimal conformation of the hypervariable domain within the flagellin molecule and, in turn, on the flagellum filament in order to display proinflammatory epitopes effectively. Flagellar genes are highly conserved among gram-negative bacteria, and much similarity in structure and function exists.