Abstract
To learn how lipooligosaccharide (LOS) phase variations affect pathogenesis, we studied two male volunteers who were challenged intraurethrally with Neisseria gonorrhoeae that make a single LOS of 3,600 daltons and sequentially followed LOS expression by gonococci as urethritis developed. LOS variation occurred in vivo. Signs and symptoms of gonorrhea began with the appearance of variants making 4,700-dalton LOS that are immunochemically similar to glycosphingolipids of human hematopoietic cells (Mandrell, R.E., J.M. Griffiss, and B.A. Macher. 1989. J. Exp. Med. 168:107) and that have acceptors for sialic acid. A variant that appeared at the onset of leukorrhoea was shed by 34/36 men with naturally acquired gonorrhea at the time they sought medical attention; the other two shed the variant associated with dysuria. None shed the challenge variant. These data show that in vivo phase shifts to higher molecular mass LOS that mimic human cell membrane glycolipids are associated with the development of gonococcal leukorrhea.
Full Text
The Full Text of this article is available as a PDF (2.5 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Apicella M. A., Mandrell R. E., Shero M., Wilson M. E., Griffiss J. M., Brooks G. F., Lammel C., Breen J. F., Rice P. A. Modification by sialic acid of Neisseria gonorrhoeae lipooligosaccharide epitope expression in human urethral exudates: an immunoelectron microscopic analysis. J Infect Dis. 1990 Aug;162(2):506–512. doi: 10.1093/infdis/162.2.506. [DOI] [PubMed] [Google Scholar]
- Caroff M., Chaby R., Karibian D., Perry J., Deprun C., Szabó L. Variations in the carbohydrate regions of Bordetella pertussis lipopolysaccharides: electrophoretic, serological, and structural features. J Bacteriol. 1990 Feb;172(2):1121–1128. doi: 10.1128/jb.172.2.1121-1128.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dudas K. C., Apicella M. A. Selection and immunochemical analysis of lipooligosaccharide mutants of Neisseria gonorrhoeae. Infect Immun. 1988 Feb;56(2):499–504. doi: 10.1128/iai.56.2.499-504.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HARKNESS A. H. The pathology of gonorrhoea. Br J Vener Dis. 1948 Dec;24(4):137–147. [PMC free article] [PubMed] [Google Scholar]
- Hitchcock P. J., Brown T. M. Morphological heterogeneity among Salmonella lipopolysaccharide chemotypes in silver-stained polyacrylamide gels. J Bacteriol. 1983 Apr;154(1):269–277. doi: 10.1128/jb.154.1.269-277.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmes K. K., Johnson D. W., Trostle H. J. An estimate of the risk of men acquiring gonorrhea by sexual contact with infected females. Am J Epidemiol. 1970 Feb;91(2):170–174. doi: 10.1093/oxfordjournals.aje.a121125. [DOI] [PubMed] [Google Scholar]
- Jennings H. J., Johnson K. G., Kenne L. The structure of an R-type oligosaccharide core obtained from some lipopolysaccharides of Neisseria meningitidis. Carbohydr Res. 1983 Sep 16;121:233–241. doi: 10.1016/0008-6215(83)84020-8. [DOI] [PubMed] [Google Scholar]
- Mandrell R. E., Griffiss J. M., Macher B. A. Lipooligosaccharides (LOS) of Neisseria gonorrhoeae and Neisseria meningitidis have components that are immunochemically similar to precursors of human blood group antigens. Carbohydrate sequence specificity of the mouse monoclonal antibodies that recognize crossreacting antigens on LOS and human erythrocytes. J Exp Med. 1988 Jul 1;168(1):107–126. doi: 10.1084/jem.168.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mandrell R. E., Lesse A. J., Sugai J. V., Shero M., Griffiss J. M., Cole J. A., Parsons N. J., Smith H., Morse S. A., Apicella M. A. In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation. J Exp Med. 1990 May 1;171(5):1649–1664. doi: 10.1084/jem.171.5.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Phillips N. J., John C. M., Reinders L. G., Gibson B. W., Apicella M. A., Griffiss J. M. Structural models for the cell surface lipooligosaccharides of Neisseria gonorrhoeae and Haemophilus influenzae. Biomed Environ Mass Spectrom. 1990 Nov;19(11):731–745. doi: 10.1002/bms.1200191112. [DOI] [PubMed] [Google Scholar]
- Schneider H., Griffiss J. M., Mandrell R. E., Jarvis G. A. Elaboration of a 3.6-kilodalton lipooligosaccharide, antibody against which is absent from human sera, is associated with serum resistance of Neisseria gonorrhoeae. Infect Immun. 1985 Dec;50(3):672–677. doi: 10.1128/iai.50.3.672-677.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneider H., Hale T. L., Zollinger W. D., Seid R. C., Jr, Hammack C. A., Griffiss J. M. Heterogeneity of molecular size and antigenic expression within lipooligosaccharides of individual strains of Neisseria gonorrhoeae and Neisseria meningitidis. Infect Immun. 1984 Sep;45(3):544–549. doi: 10.1128/iai.45.3.544-549.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneider H., Hammack C. A., Apicella M. A., Griffiss J. M. Instability of expression of lipooligosaccharides and their epitopes in Neisseria gonorrhoeae. Infect Immun. 1988 Apr;56(4):942–946. doi: 10.1128/iai.56.4.942-946.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swanson J., Barrera O., Sola J., Boslego J. Expression of outer membrane protein II by gonococci in experimental gonorrhea. J Exp Med. 1988 Dec 1;168(6):2121–2129. doi: 10.1084/jem.168.6.2121. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsai C. M., Frasch C. E. A sensitive silver stain for detecting lipopolysaccharides in polyacrylamide gels. Anal Biochem. 1982 Jan 1;119(1):115–119. doi: 10.1016/0003-2697(82)90673-x. [DOI] [PubMed] [Google Scholar]
- Weiser J. N., Love J. M., Moxon E. R. The molecular mechanism of phase variation of H. influenzae lipopolysaccharide. Cell. 1989 Nov 17;59(4):657–665. doi: 10.1016/0092-8674(89)90011-1. [DOI] [PubMed] [Google Scholar]