{"id":108,"date":"2015-11-09T20:18:04","date_gmt":"2015-11-09T20:18:04","guid":{"rendered":"https:\/\/lab.research.sickkids.ca\/howell\/?page_id=108"},"modified":"2018-04-19T09:44:02","modified_gmt":"2018-04-19T14:44:02","slug":"pnag","status":"publish","type":"page","link":"https:\/\/lab.research.sickkids.ca\/howell\/molecular-mechanisms\/exopolysaccharides\/pnag\/","title":{"rendered":"PNAG"},"content":{"rendered":"
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Model of PNAG\u00a0biosynthetic machinery<\/p>\n<\/div>

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Poly-\u03b2-1,6-N<\/em>-acetyl-D-glucosamine (PNAG) is a key virulence factor required for biofilm formation by numerous pathogenic Gram-positive and Gram-negative bacteria. The polymer has been implicated in septicemia, prosthetic joint infection, infective endocarditis, urinary tract infections, whopping cough, and neonatal bacteremia. Partial deacetylation of PNAG (dPNAG) is required for the structural development and integrity of the biofilm. De-N<\/em>-acetylation of PNAG occurs in the periplasm in Gram-negative species, and deletion of the deacetylase gene has different effects depending on the organism. For example, E. coli <\/em>strains lacking pgaB <\/em>cannot export PNAG from the cell, while Bordetella bronchiseptica bpsB <\/em>deletion strains have a biofilm-defective phenotype and significantly altered biofilm architecture. In contrast, in Gram-positive species deacetylation occurs extracellularly, and deletion of the deacetylase icaB<\/em> results in shedding of the polymer from the cell surface. As a result strains that lack the deacetylase have highly attenuated virulence.<\/p>\n

Given the importance of this chemical modification for biofilm formation, we have focused our efforts on understanding the structure and function of the deacetylase enzymes, PgaB, BpsB and IcaB from E. coli, B. bronchiseptica,<\/em> and S. epidermidis,<\/em> respectively. Structural analyses have shed light on unique features of each enzyme and have suggested a role for C-terminal domain of PgaB\/BpsB in both efficient deacetylation and polymer export.<\/p>\n<\/div>

Current projects<\/h2>\n

Ongoing projects are focused on:<\/p>\n