Motility and chemotaxis in Campylobacter and Helicobacter

Abstract

Flagellar motility of Campylobacter jejuni and Helicobacter pylori influences host colonization by promoting migration through viscous milieus such as gastrointestinal mucus. This review explores mechanisms C. jejuni and H. pylori employ to control flagellar biosynthesis and chemotactic responses. These microbes tightly control the activities of σ(54) and σ(28) to mediate ordered flagellar gene expression. In addition to phase-variable and posttranslational mechanisms, flagellar biosynthesis is regulated spatially and numerically so that only a certain number of organelles are placed at polar sites. To mediate chemotaxis, C. jejuni and H. pylori combine basic chemotaxis signal transduction components with several accessory proteins. H. pylori is unusual in that it lacks a methylation-based adaptation system and produces multiple CheV coupling proteins. Chemoreceptors in these bacteria contain nonconserved ligand binding domains, with several chemoreceptors matched to environmental signals. Together, these mechanisms allow for swimming motility that is essential for colonization.

Figure 1

Structure of the flagellar organelle of Campylobacter jejuni and Helicobacter pylori. The major components common to the flagella of C. jejuni and H. pylori are shown. Other relatively less-characterized proteins specific to each bacterium are not shown for simplicity. Flagellar components are color-coded based on the classification of the respective genes in the transcriptional regulatory cascade for the organisms: red (class 1), blue (class 2), and green (class 3). An exception includes flaB, which is a σ⁵⁴-dependent class 2 gene. Proteins in gray include those encoded by genes whose transcription has not been analyzed or is known to be outside the flagellar transcriptional hierarchy. Other class 1 proteins that are required for expression of σ⁵⁴-dependent class 2 genes but are not part of the flagellar structure are not shown. Abbreviation: T3SS, type III secretion system.

Figure 2

The flagellar transcriptional regulatory cascade for Campylobacter jejuni and Helicobacter pylori. The flagellar genes and respective proteins included in the flagellar transcriptional cascade are shown. These factors are color-coded on the basis of their classification in the transcriptional regulatory cascade: red (class 1 genes), blue (class 2 genes), and green (class 3 genes). fliA (encoding σ²⁸) and flgM are included as class 2 genes in C. jejuni, but these genes are dependent only partially on σ⁵⁴ for expression. Formation of the flagellar T3SS (which is composed of FlhA, FlhB, FliO, FliP, FliQ, and FliR) has been proposed to create a signal detected by the FlgS sensor kinase, resulting in autophosphorylation of the protein. Phosphotransfer to the FlgR response regulator activates the protein, allowing for interactions with and stimulation of σ⁵⁴. The FlhF GTPase is likely involved in a separate pathway that converges with or functions downstream of the FlgSR-T3SS pathway to fully activate expression of σ⁵⁴-dependent class 2 genes. The T3SS facilitates the ordered secretion of the class 2 rod, ring, and hook proteins to complete the HBB complex. Secretion of the antisigma factor FlgM through the HBB complex relieves repression of σ²⁸ activity, resulting in expression of class 3 genes. The class 3 genes include flaA, which encodes the major flagellin, and those for other minor filament proteins. Other class 3 genes of C. jejuni appear to encode proteins not involved in motility and, instead, may be involved in virulence or colonization of C. jejuni. Abbreviations: HBB, hook-basal body; T3SS, type III secretion system.

Figure 3

Chemotaxis signal transduction systems of Campylobacter jejuni and Helicobacter pylori. Transmembrane chemoreceptors are shown as purple and red bars interacting with the coupling proteins CheW (W) or CheV (V). H. pylori contains three CheV proteins, termed CheV1 (V1), CheV2 (V2), and CheV3 (V3). The coupling proteins in turn interact with CheA, also called CheAY (AY), which catalyzes a kinase reaction using ATP as the phosphodonor. The phosphoryl group is passed to CheY (Y) and removed by CheZ (Z). C. jejuni contains CheR (R) and CheB (B), which methylate and demethylate, respectively, the chemoreceptors in other microbes. H. pylori and C. jejuni also contain cytoplasmic chemoreceptors that are not shown but are presumed to participate in the same protein-protein interactions.