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Alginate biosynthesis protein Alg8 is an essential inner-membrane glycosyltransferase in Pseudomonas aeruginosa that serves as the catalytic subunit for alginate polymerization (MDPI, https://www.mdpi.com/2076-2607/11/12/2833; NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1346658/). It utilizes GDP-mannurate as a substrate to synthesize long chains of polymannuronate, which are subsequently modified and secreted to form the alginate exopolysaccharide (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135710/). Alginate is a primary component of the biofilm matrix in mucoid P. aeruginosa strains, which are hallmark pathogens in the lungs of cystic fibrosis patients (Microbiology Society, https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.2007/016063-0). This protective matrix shields the bacteria from the host immune system and significantly increases resistance to antibiotic therapy (ACS, https://pubs.acs.org/doi/10.1021/acsinfecdis.0c00018). Because Alg8 is a bottleneck in the alginate production pathway, it is considered a high-priority target for the development of anti-virulence drugs designed to disrupt biofilm formation and restore antibiotic efficacy (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1346658/).
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