Pseudomonas aeruginosa flagellin (FliC) (FliC)

Pseudomonas aeruginosa flagellin, primarily encoded by the fliC gene, is the principal structural subunit of the bacterial flagellum and is essential for motility, chemotaxis, and host colonization (UniProt P02968). As a potent pathogen-associated molecular pattern (PAMP), it is recognized by the host's innate immune system through Toll-like receptor 5 (TLR5) on the cell surface and the NLRC4 inflammasome intracellularly (PubMed: 17512984). This recognition triggers a robust pro-inflammatory cascade, including the release of cytokines like IL-8 and IL-1β, which are critical for early defense but can contribute to tissue damage in chronic infections (PubMed: 11564765). In drug development, flagellin is targeted as a vaccine antigen to induce protective immunity and as a target for monoclonal antibodies designed to inhibit bacterial dissemination. Furthermore, its ability to strongly activate TLR5 has led to its investigation as a potent mucosal adjuvant for various recombinant vaccines (PubMed: 19017787). However, the existence of two distinct serotypes, Type A and Type B, and the risk of inducing a systemic inflammatory response present significant challenges for universal therapeutic application. Effective targeting of flagellin remains a high priority for managing multi-drug resistant Pseudomonas infections in vulnerable populations, such as those with cystic fibrosis or severe burns (PubMed: 11133824).

Other names

Flagellar filament structural proteinH-antigenFlagellin type AFlagellin type BFliC protein

Flagellin acts as a potent agonist of Toll-like receptor 5 (TLR5), triggering the MyD88-dependent signaling pathway to induce pro-inflammatory cytokines. In vaccine applications, it serves as a primary antigen for the induction of neutralizing antibodies that inhibit bacterial motility and as an adjuvant to enhance systemic and mucosal immunity. Therapeutic antibodies target flagellin to neutralize its ability to facilitate bacterial spread and to prevent excessive TLR5-mediated inflammation in the host.