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Salmonella enterica biofilm matrix polysaccharides, primarily cellulose, colanic acid, and O-antigen capsule, are critical components of the extracellular polymeric substances (EPS) that encase bacterial communities (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901215/). Cellulose, a beta-1,4-linked D-glucose polymer, provides structural stability and protects the bacteria from environmental stressors such as desiccation, UV radiation, and antimicrobial agents (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811568/; RSC, https://pubs.rsc.org/en/content/chapter/9781837674930/00123). These polysaccharides facilitate chronic persistence, notably in the gallbladder during typhoid fever, by shielding the pathogen from the host immune system and reducing antibiotic penetration (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901215/). In the rdar (red, dry, and rough) morphotype, cellulose and curli fimbriae interact to form a robust, resistant network (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1482990/). Therapeutic strategies targeting these polysaccharides include enzymatic degradation by cellulases or the use of small molecules like 2-aminoimidazoles and procyanidins to inhibit their synthesis (RSC, https://pubs.rsc.org/en/content/chapter/9781837674930/00123; NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237244/). However, a significant therapeutic challenge exists as cellulose also acts as an anti-virulence factor; its removal can lead to increased flagellar motility and enhanced epithelial invasion, potentially exacerbating acute infection (KU Leuven, https://www.kuleuven.be/doctoraatsverdediging/fiches/3E18/3E180592.htm).
Enzymatic degradation of the polysaccharide matrix or inhibition of biosynthetic pathways (e.g., Bcs complex or CsgD regulator) to disrupt biofilm integrity and enhance antibiotic penetration.
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