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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 (alpha 2right-arrow 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 (alpha 2right-arrow8)-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 alpha 2,3 sialyltransferase gene, lst, increased sensitivity to 50% NHS. In contrast, replacement of the lacto-N-neotetraose alpha -chain (Galbeta 1-4GlcNAcbeta 1-3Galbeta 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)right-arrowKDO2right-arrowlipid A LOS without an alpha -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 Hep2right-arrowKDO2right-arrowlipid A and KDO2right-arrowlipid 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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