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Pseudomonas aeruginosa alginate is a linear exopolysaccharide composed of 1,4-linked β-D-mannuronic acid and its C5-epimer α-L-guluronic acid (Franklin et al., 2011). It is the defining characteristic of the mucoid phenotype of P. aeruginosa, which is strongly associated with chronic lung infections in patients with cystic fibrosis (Govan & Deretic, 1996). Alginate functions as a key structural component of the bacterial biofilm, providing a protective scaffold that shields the pathogen from host immune defenses, such as phagocytosis and complement-mediated killing, and limits the penetration of many antibiotics (Hentzer et al., 2001). Furthermore, it acts as an antioxidant, protecting the bacteria from reactive oxygen species produced by host neutrophils (Learn et al., 1987). Therapeutic interventions targeting alginate aim to degrade the polymer using enzymes like alginate lyase or to neutralize it with specific antibodies to enhance bacterial clearance and antibiotic efficacy (Lyczak et al., 2002). Clinical candidates like OligoG work by interfering with the electrostatic interactions of alginate, thereby reducing the viscosity of infected mucus and disrupting the biofilm matrix (Powell et al., 2013).
Enzymatic degradation of the polysaccharide chain to reduce biofilm viscosity and enhance antibiotic penetration; opsonization by antibodies to promote phagocytic clearance (Powell et al., 2013; Lyczak et al., 2002).
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