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Infection and Immunity, December 1998, p. 5939-5947, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
The (
2
8)-Linked Polysialic Acid Capsule and
Lipooligosaccharide Structure Both Contribute to the Ability of
Serogroup B Neisseria meningitidis To Resist the
Bactericidal Activity of Normal Human Serum
C. M.
Kahler,1
L. E.
Martin,1
G. C.
Shih,1,2
M. M.
Rahman,3
R. W.
Carlson,3 and
D. S.
Stephens1,2,4,*
Departments of
Medicine1 and
Microbiology and
Immunology,2
Emory University School of
Medicine, and VA Medical Center,4 Atlanta,
Georgia 30033, and
the Complex Carbohydrate Research
Center, University of Georgia, Athens, Georgia 306023
Received 28 July 1998/Returned for modification 28 August
1998/Accepted 23 September 1998
The molecular basis for the resistance of serogroup B
Neisseria meningitidis to the bactericidal activity of
normal human sera (NHS) was examined with a NHS-resistant, invasive
serogroup B meningococcal isolate and genetically and structurally
defined capsule-, lipooligosaccharide (LOS)-, and sialylation-altered mutants of the wild-type strain. Expression of the (
2
8)-linked polysialic acid serogroup B capsule was essential for meningococcal resistance to NHS. The very NHS-sensitive phenotype of acapsular mutants (99.9 to 100% killed in 10, 25, and 50% NHS) was not rescued by complete LOS sialylation or changes in LOS structure. However, expression of the capsule was necessary but not sufficient for a fully
NHS-resistant phenotype. In an encapsulated background, loss of LOS
sialylation by interrupting the
2,3 sialyltransferase gene,
lst, increased sensitivity to 50% NHS. In contrast,
replacement of the lacto-N-neotetraose
-chain
(Gal
1-4GlcNAc
1-3Gal
1-4Glc) with glucose extensions
(GlcN) in a galE mutant resulted in a strain
resistant to killing by 50% NHS at all time points. Encapsulated meningococci expressing a
Hep2(GlcNAc)
KDO2
lipid A LOS without an
-chain demonstrated enhanced sensitivity to 50% NHS (98%
killed at 30 min) mediated through the antibody-dependent classical
complement pathway. Encapsulated LOS mutants expressing truncated
Hep2
KDO2
lipid A and
KDO2
lipid A structures were also sensitive to 50%
NHS (98 to 100% killed at 30 min) but, unlike the wild-type strain and mutants with larger oligosaccharide structures, they were killed by
hypogammaglobulinemic sera. These data indicate that encapsulation is
essential but that the LOS structure contributes to the ability of
serogroup B N. meningitidis to resist the
bactericidal activity of NHS.
*
Corresponding author. Mailing address: Division of
Infectious Diseases, Department of Medicine, 69 Butler St.,
SE, Atlanta, GA 30303. Phone: (404) 728-7688. Fax: (404) 329-2210. E-mail: dstep01{at}emory.edu.
Infection and Immunity, December 1998, p. 5939-5947, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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