Disease relevance of flaB

• Sequences of three gene fragments (flaA, flaB, and vacA) from Helicobacter pylori strains isolated from patients in Germany, Canada, and South Africa were analyzed for diversity and for linkage equilibrium by using the Homoplasy Test and compatibility matrices [1].
• The lpp20 gene encoding this protein was cloned in Escherichia coli by using the vector lambda EMBL3, and plasmid subclones expressed the full-length protein from the native H. pylori promoter. lpp20 was mapped to the same 358-kb NruI fragment as flaB [2].
• The flagellin proteins in pathogenic bacteria such as Campylobacter jejuni and Helicobacter pylori are heavily glycosylated with the nine-carbon alpha-keto acid, pseudaminic acid [3].
• Bacterial flagellin, the primary structural component of flagella, is a dominant target of humoral immunity upon infection by enteric pathogens and in Crohn's disease [4].
• Whereas neither oral nor rectal administration of flagellin elicited a strong serum Ab response, induction of colitis with dextran sodium sulfate resulted in a MyD88-dependent serum Ab response to endogenous flagellin, suggesting that, in an inflammatory milieu, TLR signaling promotes acquisition of Abs to intestinal flagellin [4].

High impact information on flaB

• In contrast to Ab responses to whole flagella (H serotyping), responses to flagellin monomers displayed only moderate serospecificity [4].
• Thus, acquisition of a humoral immune response to flagellin requires activation of innate immunity, is T cell dependent, and can originate from flagellin in the intestinal tract in inflammatory conditions in the intestine [4].
• Humoral immune response to flagellin requires T cells and activation of innate immunity [4].
• Structural, genetic and functional characterization of the flagellin glycosylation process in Helicobacter pylori [5].
• Insertional mutagenesis of four of these homologues in Helicobacter (HP0178, HP0326A, HP0326B, HP0114) resulted in a non-motile phenotype, no structural flagella filament and only minor amounts of flagellin protein detectable by Western immunoblot [5].

Chemical compound and disease context of flaB

• A causative agent of gastric and duodenal ulcers, H. pylori, heavily modifies its flagellin with the sialic acid-like sugar 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-alpha-l-manno-nonulosonic acid (pseudaminic acid) [6].

Biological context of flaB

• As little as 42 bp of DNA upstream of the flaB promoter and 26 bp of DNA sequence downstream of the transcriptional start site were sufficient for efficient FlgR-mediated expression from a flaB'-'xylE reporter gene in H. pylori, indicating that FlgR does not use an enhancer to activate transcription [7].
• Topoisomerase I of Helicobacter pylori: juxtaposition with a flagellin gene (flaB) and functional requirement of a fourth zinc finger motif [8].
• Mapping of the transcription start site for the H. pylori flaB gene by a primer extension experiment confirmed the functional activity of the sigma 54 promoter [9].
• Isogenic flaA and flaB mutants of H. mustelae F1 were constructed by means of reverse genetics [10].
• Helicobacter pylori possesses two different flagellin genes, flaA and flaB, which are unlinked on the chromosome and transcribed from sigma(28) and sigma(54) promoters, respectively [11].

Anatomical context of flaB

• In this study we analyzed whether infection with Helicobacter pylori gives rise to specific B-cell responses against a number of putative virulence factors of H. pylori, e.g., urease, flagellin, and different bacterial surface antigens, locally in the gastric mucosa [12].
• Among these, expression of the genes for the neutrophil activating protein (napA) and the major flagellin subunit (flaA) were significantly induced [13].
• Salmonella enterica serovar Typhimurium FliC flagellin was able to activate human gastric epithelial cells [14].

Associations of flaB with chemical compounds

• Isogenic mutant strains of H. mustelae have been constructed by disruption of the flaA or flaB gene with a kanamycin resistance cassette or by introduction of both a kanamycin and a chloramphenicol resistance gene to produce a double mutant [15].
• The minor 57,000-Mr flagellin species contained a higher content of proline [16].

Other interactions of flaB

• The double-mutant strain was unable to colonize; the flaA and flaB single-mutant strains were able to initially colonize at a low level and establish persistent infection with increasing numbers of organisms over time [15].
• In the isogenic mutant of rpoN, transcription of the flaB gene was severely affected, but transcription of the ureA gene (control) was intact [17].

Analytical, diagnostic and therapeutic context of flaB

• However, Western blot analysis showed substantially reduced amounts of the major flagellin subunit FlaA in the H. pylori 11A ylxH knockout compared to H. pylori 11A [18].
• A marker strain with wild-type phenotype, carrying multiple plasmid-borne copies of gfp under the control of the H. pylori flaB promoter, was constructed for studies of bacterial distribution and transmission in animal models [19].
• Sequence alignment of H. pylori flagellin (FlaA) with other bacterial flagellins demonstrates a high degree of similarity in the amino-terminal and carboxy-terminal regions, including those of the closely related genus Campylobacter (56% overall identity with Campylobacter coli flaA), but little homology in the central domain [20].
• Flagella of Campylobacter pylori were analyzed by electron microscopy and purified, and the molecular weight of the flagellin was determined [21].
• Using three different reporter genes as well as Northern blot analyses and RT-PCR, it was determined that both flagellin genes are transcribed in a growth phase-dependent fashion [11].

References