Periplasmic depolymerase provides insight into ABC transporter-dependent secretion of bacterial capsular polysaccharides

Significance Capsules are critical virulence determinants for bacterial pathogens. They are composed of capsular polysaccharides (CPSs) with diverse structures, whose assembly on the cell surface is often powered by a conserved ABC transporter. Current capsule-assembly models include a contiguous trans-envelope channel directing nascent CPSs from the transporter to the cell surface. This conserved apparatus is an attractive target for antivirulence antimicrobial development. This work describes a CPS depolymerizing lyase enzyme found in the Burkholderiales and unique structural features that define its mechanism, CPS specificity, and evolution to function in the periplasm in a noncatabolic role. The activity of this enzyme provides evidence that CPS assembled in an ABC transporter-dependent system is exposed to periplasm during translocation to the cell surface.