Pseudomonas aeruginosa surface adhesins

Pseudomonas aeruginosa surface adhesins are a diverse array of proteinaceous and non-proteinaceous structures on the bacterial cell surface that mediate attachment to host tissues and abiotic surfaces. Primary components include Type IV pili, which facilitate twitching motility and initial attachment, and flagella, which provide swimming motility and bind to host mucins and glycolipids [1][2]. Additionally, the bacterium produces soluble lectins, LecA (PA-IL) and LecB (PA-IIL), which localize to the outer membrane and bind specifically to galactose and fucose/mannose residues, respectively, playing a vital role in biofilm maturation and host cell cytotoxicity [3][4]. These adhesins are fundamental to the pathogenesis of P. aeruginosa, enabling the colonization of the respiratory tract in cystic fibrosis patients and the formation of protective biofilms in chronic infections [5]. Targeting these molecules with glycomimetics or monoclonal antibodies offers a promising anti-adhesion strategy to prevent or treat infections while minimizing the selective pressure that leads to multi-drug resistance [6][7]. By blocking the initial tethering of the pathogen to the host, these therapies can potentially reduce the severity of infections and enhance the efficacy of co-administered antibiotics. [1] Burrows, L. L. (2012). Pseudomonas aeruginosa Type IV Pili. Annu Rev Microbiol. [2] Haiko, J., & Westerlund-Wikström, B. (2013). The Role of the Bacterial Flagellum in Adhesion and Virulence. Biology. [3] Blanchard, B., et al. (2008). Structure of LecA, a lectin from Pseudomonas aeruginosa. Proteins. [4] Mitchell, E., et al. (2002). Structural basis for oligosaccharide-mediated adhesion of Pseudomonas aeruginosa to host cells. Nature Structural Biology. [5] Filloux, A., & Sagampoc, D. (2021). Pseudomonas aeruginosa Virulence Factors. Microbiology Spectrum. [6] Zannoni, A., et al. (2022). Glycomimetics as inhibitors of Pseudomonas aeruginosa lectins. Drug Discovery Today. [7] DiGiandomenico, A., et al. (2014). A multifunctional bispecific antibody protects against Pseudomonas aeruginosa. Science Translational Medicine.

Other names

P. aeruginosa adhesinsBacterial attachment factorsPseudomonas fimbriaePA-IL and PA-IIL lectins

The mechanism of action involves the competitive inhibition of bacterial attachment to host cell receptors. Small molecule glycomimetics bind to the carbohydrate-recognition domains of lectins like LecA and LecB, preventing them from cross-linking host glycans and stabilizing the biofilm matrix. Monoclonal antibodies target structural proteins such as pilin (PilA) or flagellin (FliC), physically blocking the interaction between these appendages and host surfaces, thereby inhibiting colonization and motility-driven spread.