KpsF Is the Arabinose-5-phosphate Isomerase Required for 3-Deoxy-d-manno-octulosonic Acid Biosynthesis and for Both Lipooligosaccharide Assembly and Capsular Polysaccharide Expression in Neisseria meningitidis

We have identified and defined the function ofkpsF of Neisseria meningitidis and the homologues of kpsF in encapsulated K1 and K5Escherichia coli. KpsF was shown to be the arabinose-5-phosphate isomerase, an enzyme not previously identified in prokaryotes, that mediates the interconversion of ribulose 5-phosphate and arabinose 5-phosphate. KpsF is required for 3-deoxy-d-manno-octulosonic acid (Kdo) biosynthesis inN. meningitidis. Mutation of kpsF or the gene encoding the CMP-Kdo synthetase (kpsU/kdsB) inN. meningitidis resulted in expression of a lipooligosaccharide (LOS) structure that contained only lipid A and reduced capsule expression in the five invasive disease-associated meningococcal serogroups (A, B, C, Y, and W-135). The step linking meningococcal capsule and LOS biosynthesis was shown to be Kdo production as the expression of capsule was wild type in a Kdo transferase (kdtA) mutant. Thus, in addition to lipooligosaccharide assembly, Kdo is required for meningococcal capsular polysaccharide expression. Furthermore, N. meningitidis, unlike enteric Gram-negative bacteria, can survive and synthesize only unglycosylated lipid A.