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Pseudomonas aeruginosa O-antigen lipopolysaccharide is the distal, highly variable carbohydrate component of the lipopolysaccharide (LPS) molecule located on the outer membrane of this Gram-negative pathogen (King et al., 2009, PubMed: 19129351). It serves as a critical virulence factor by protecting the bacterium from host complement-mediated killing and providing a barrier against antimicrobial peptides (Lam et al., 2011, PubMed: 21414841). The O-antigen is composed of repeating oligosaccharide units that define the International Antigenic Typing Scheme (IATS) serotypes, of which there are 20 recognized varieties (Rocchetta et al., 1999, PubMed: 10515902). In clinical settings, it is a primary target for the development of monoclonal antibodies and conjugate vaccines, such as Panobacumab, which aim to enhance opsonophagocytic killing of the bacteria (Que et al., 2014, PubMed: 24415639). However, the high structural diversity between serotypes and the tendency of P. aeruginosa to lose O-antigen expression during chronic infections (transitioning to a "rough" phenotype) present significant challenges for broad-spectrum therapeutic efficacy (Huszczynski et al., 2020, PubMed: 31843936).
Opsonophagocytic killing (OPK), endotoxin neutralization, and inhibition of bacterial adhesion.
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