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PilA is the major structural subunit of Type IV pili (Tfp) in non-typeable Haemophilus influenzae (NTHi), a Gram-negative bacterium that is a common commensal of the human nasopharynx but also a significant opportunistic pathogen (Novotny et al., 2015). Tfp are hair-like appendages on the bacterial surface that play critical roles in adherence to host respiratory epithelial cells, twitching motility, natural transformation (competence), and the formation and stability of biofilms (Jurcisek et al., 2007; Bakaletz, 2018). In the context of disease, NTHi is a leading cause of acute otitis media in children and acute exacerbations of chronic obstructive pulmonary disease (COPD) in adults (Wilkinson et al., 2022). PilA is a primary target for therapeutic intervention, particularly as a vaccine candidate, because it is highly conserved across NTHi strains and essential for colonization and persistence (Novotny et al., 2015). Experimental vaccines using recombinant soluble PilA (rsPilA) or fusion proteins (such as PE-PilA) have shown the ability to elicit antibodies that not only prevent NTHi adherence but also actively disperse established biofilms, thereby increasing the susceptibility of the bacteria to host immune defenses and traditional antibiotics (Bakaletz, 2018; Wilkinson et al., 2022). The development of PilA-targeted therapies represents a promising strategy to reduce the burden of chronic and recurrent respiratory infections caused by NTHi (Novotny et al., 2015).
Induction of antibodies that inhibit bacterial adherence to host cells and promote the dispersal of bacterial biofilms
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