title: Flagellar localization of a Helicobacter pylori autotransporter protein.
abstract: Helicobacter pylori contains four genes that are predicted to encode proteins secreted by the autotransporter (type V) pathway. One of these, the pore-forming toxin VacA, has been studied in great detail, but thus far there has been very little investigation of three VacA-like proteins. We show here that all three VacA-like proteins are >250 kDa in mass and localized on the surface of H. pylori. The expression of the three vacA-like genes is upregulated during H. pylori colonization of the mouse stomach compared to H. pylori growth in vitro, and a wild-type H. pylori strain outcompeted each of the three corresponding isogenic mutant strains in its ability to colonize the mouse stomach. One of the VacA-like proteins localizes to a sheath that overlies the flagellar filament and bulb, and therefore, we designate it FaaA (flagella-associated autotransporter A). In comparison to a wild-type H. pylori strain, an isogenic faaA mutant strain exhibits decreased motility, decreased flagellar stability, and an increased proportion of flagella in a nonpolar site. The flagellar localization of FaaA differs markedly from the localization of other known autotransporters, and the current results reveal an important role of FaaA in flagellar localization and motility.
  
  
  OBJECTIVE
  The pathogenesis of most bacterial infections is dependent on the actions of secreted proteins, and proteins secreted by the autotransporter pathway constitute the largest family of secreted proteins in pathogenic Gram-negative bacteria. In this study, we analyzed three autotransporter proteins (VacA-like proteins) produced by Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach and contributes to the pathogenesis of gastric cancer and peptic ulcer disease. We demonstrate that these three proteins each enhance the capacity of H. pylori to colonize the stomach. Unexpectedly, one of these proteins (FaaA) is localized to a sheath that overlies H. pylori flagella. The absence of FaaA results in decreased H. pylori motility as well as a reduction in flagellar stability and a change in flagellar localization. The atypical localization of FaaA reflects a specialized function of this autotransporter designed to optimize H. pylori colonization of the gastric niche.
authors.affiliation: Department of Medicine, Vanderbilt University, School of Medicine, Nashville, Tennessee, USA.
authors.forename: Jana N
authors.initials: JN
authors.lastname: Radin
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gaddy
authors.forename: Christian
authors.initials: C
authors.lastname: González-Rivera
authors.forename: John T
authors.initials: JT
authors.lastname: Loh
authors.forename: Holly M Scott
authors.initials: HM
authors.lastname: Algood
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cover
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis* / Q000737:chemistry; D004195:Disease Models, Animal; D005407:Flagella / Q000737:chemistry* / Q000502:physiology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000737:chemistry* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008124:Locomotion; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis* / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D013270:Stomach / Q000382:microbiology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins