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Pseudomonas aeruginosa surface polysaccharides, most notably lipopolysaccharides (LPS), are essential structural components of the Gram-negative outer membrane that play a dual role as virulence factors and primary receptors for bacteriophages. LPS is composed of three distinct regions: the hydrophobic Lipid A, a core oligosaccharide, and the distal O-antigen (Source: Wikipedia, Lipopolysaccharide). These molecules provide a physical barrier against antibiotics and host immune defenses while facilitating bacterial attachment to host tissues. In phage therapy, the specific recognition of O-antigen or core structures by phage tail fibers is the first and most critical step in the infection cycle (Source: Frontiers in Microbiology, doi:10.3389/fmicb.2018.01837). Because P. aeruginosa exhibits significant O-antigen diversity across different strains, these polysaccharides are major determinants of phage host range. Targeting these structures is a primary focus for developing novel antibacterial strategies, including phage cocktails and LPS-neutralizing agents, to combat multi-drug resistant infections.
Bacteriophages utilize these polysaccharides as primary docking sites, where tail fibers bind to specific O-antigen or core oligosaccharide motifs to initiate DNA injection and subsequent bacterial lysis (Source: PubMed, PMID: 30108563). Polymyxins bind to the Lipid A component of LPS, disrupting the outer membrane and increasing permeability (Source: StatPearls, NBK557775).
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