FIG 10.

Model for the roles of the F. tularensis WaaY, WaaZ, and WaaL proteins in LPS biosynthesis. In general, LPS is synthesized as two separate components: (i) lipid A-core sugars and (ii) polymers of O-antigen subunits. O-antigen sugars are synthesized in the cytoplasm and assembled onto a lipid carrier, i.e., the undecaprenol pyrophosphate that is associated with WbaP or PNPT, polyisoprenyl-phosphate hexose-1-phosphate transferase, or N-acetylhexosamine-1-phosphate transferase. The Wzx protein flips the charged lipid carrier, with the assembled O-antigen unit, through the inner membrane from the cytoplasm to the periplasmic space. Repeating O-antigen subunits are polymerized on the lipid carrier by the Wzy protein. The lipid A portion of LPS is synthesized by a number of Lpt and Lpx proteins on the inner leaflet of the inner membrane. Waa proteins (WaaY and WaaZ) transfer or modify core sugars to the lipid A molecule as they help to assemble the core structure of LPS. ValA and LptB transport the lipid A-core sugars to the outer leaflet of the inner membrane, where O-antigen subunits are added by the O-antigen ligase, WaaL, and then they are chaperoned to the outer membrane by LptA and LptD/RlpB (55). F. tularensis mutants that are disrupted for WaaY and WaaZ production are depicted with truncated cores, while the lipid A-core sugar structure of an F. tularensis waaL mutant would be the same as that of wild-type Schu S4 but lacking O-antigen subunits, since the WaaL protein performs this ligation function.