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J. Biol. Chem., Vol. 277, Issue 27, 24103-24113, July 5, 2002
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From the We have identified and defined the function of
kpsF of Neisseria meningitidis and the
homologues of kpsF in encapsulated K1 and K5
Escherichia 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 in
N. meningitidis. Mutation of kpsF or the gene
encoding the CMP-Kdo synthetase (kpsU/kdsB) in
N. 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.
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*
,,
,**
Division of Infectious Diseases, Department
of Medicine, Emory University School of Medicine, the
** Department of Veterans Affairs Medical Center,
Atlanta, Georgia 30033, the § Complex Carbohydrate
Research Center, University of Georgia, Athens, Georgia 30602, and
the ¶ Department of Medicinal Chemistry, University of Michigan,
Ann Arbor, Michigan 48109
*
This work was supported by United States Public Health
Service Grants AI-33517 and AI40247 from the National Institutes of Health (to D. S. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Vertex Pharmaceuticals, Inc., 130 Waverly
St., Cambridge, MA 02139.
To whom correspondence should be addressed:
Division of Infectious Diseases, Dept. of Medicine, Emory
University School of Medicine, 69 Butler St., S.E., Atlanta, GA
30303. Tel.: 404-728-7688; Fax: 404-329-2210; Email:
dstep01@emory.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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