Disease relevance of flaA

• AIM: To testify the immunogenicity of a conservative B-cell linear epitope of Helicobacter pylori (H pylori) flagellin A [1].
• 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 [2].
• 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 [3].
• 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 [3].
• 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) [4].

High impact information on flaA

• In contrast to Ab responses to whole flagella (H serotyping), responses to flagellin monomers displayed only moderate serospecificity [3].
• 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 [3].
• Natural transformation of competent H. pylori strains with plasmid constructs harbouring a catGC-inactivated flaA gene resulted in chloramphenicol-resistant transformants at an average frequency of 4 x 10(-5) [5].
• The region upstream of the flaA promoter is subject to local DNA modification, resulting in the masking of two out of three closely linked HindIII restriction sites in the chromosome of strain 898-1 [6].
• The down-regulation of flaA, sodB, and HP0874 was confirmed by quantitative PCR, and the down-regulation of omp11 was confirmed by RT-PCR [7].

Biological context of flaA

• The H. pylori isolates from the four experimentally infected cats had restriction fragment length polymorphism patterns specific for the flaA gene that were identical to those of the inoculating strain [8].
• Isogenic flaA and flaB mutants of H. mustelae F1 were constructed by means of reverse genetics [9].
• In flaA gene sequencing, these identical and similar isolates showed close sequence similarity between the antrum and body, whereas different isolate showed 31 points of different nucleotide sequences [10].
• By contrast, the flaA gene blot hybridization profiles were more diverse and consistent with greater variation at restriction sites in adjacent regions of the genome [11].
• No consistent associations were observed for selected strain subsets between the DdeI flaA profiles and phenotype (motility and cytotoxicity), urease gene profile or patient symptomatology [11].

Anatomical context of flaA

• CONCLUSION: The conservative short fragment NDSDGR is the core of a linear B-cell epitope of flagellin A [1].
• Weakly positive motility tests of the flaA mutants correlated with the existence of short truncated flagella [9].
• Humoral immune response to flagellin requires T cells and activation of innate immunity [3].

Associations of flaA 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 [12].

Other interactions of flaA

• 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 [12].
• Bacterial isolates were typed with random amplified polymorphic DNA and PCR-restriction fragment length polymorphism of the genes ureA-B, glmM, or flaA [13].

Analytical, diagnostic and therapeutic context of flaA

• 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 [14].
• Sequence analysis of the flaA flanking regions and mapping of the flaA mRNA start site by a primer extension experiment indicated that transcription of the gene is under the control of a sigma 28-specific promoter sequence in H. pylori [6].
• We compared the genotypes of paired-isolates by random arbitrarily primed polymerase chain reaction (PCR), flagella gene PCR-based restriction fragment length polymorphism, and flaA gene sequencing [10].

References