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| Pathogenesis of human infection by pathogenic Neisseria and Haemophilus | ||||||
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Our laboratory is committed to studies on the mechanisms of pathogenesis of Neisseria gonorrhoeae, N. meningitidis and Haemophilus influenzae. Specifically, we are focusing on the role that the lipooligosaccharides (a surface glycolipid) of these microbes play in the pathogenesis of human infections. In addition, we are engaged in studies to elucidate the nature of the human immune response to these lipooligosaccharides. Our major emphasis at the present time is elucidation of the genetic basis of the biosynthetic pathways responsible for the synthesis of the oligosaccharide portions of these glycolipids. We have developed a family of lipooligosaccharide mutants in N. gonorrhoeae and H. influenzae induced either with phage-like particles or transposons. These mutants are being used to study the role of the carbohydrate portion of these glycolipids in pathogenesis. These studies are indicating that these bacteria invade human cells by attachment of the glycolipid saccharide component to receptors used by the human cell for transport of glycoproteins. We are currently studying the process by which this proceeds and determining if the bacterial cell communicates with the human cell to induce production of these receptors.
Another important component of our work is the chemical analysis of the carbohydrate structure of these glycolipids. These studies have demonstrated that the saccharide portion contains structures which mimic human antigens. At least three different important human cell surface antigens can be mimicked by the saccharide portion of the glycolipids of N. gonorrhoeae and H. influenzae. This mimicry may be important in immune evasion by the bacteria. |
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| Selected Publications | ||||||
| Click Here for a Complete List of Articles | ||||||
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Falsetta, M.L., Bair, T.B., Ku, S.C., Vanden Hoven, R.N., Steichen, C.T., McEwan, A.G., Jennings, M.P., and Apicella M.A. Transcriptional profiling identifies the metabolic phenotype of gonococcal biofilms. Infect Immun.77(9):3522-32,2009.
Neil, R.B., and Apicella M.A. Clinical and laboratory evidence for Neisseria meningitidis biofilms. Future Microbiol. 4:555-63, 2009. Review. Neil, R.B., and Apicella M.A. Role of HrpA in biofilm formation of Neisseria meningitidis and regulation of the hrpBAS transcripts. Infect Immun. 77(6):2285-93, 2009. Apicella M.A. Bacterial otitis media, the chinchilla middle ear, and biofilms. Invited Editorial Commentary. Journal of Infectious Diseases. 199:774-775, 2009. Brock Neil, R., Shao, J.Q., and Apicella M.A. Biofilm formation on human airway epithelia by encapsulated Neisseria meningitidis serogroup B. Microbes Infect. 11(2):281-7, 2009. Steichen, C.T., Shao, J.Q., Ketterer, M.R., and Apicella M.A. Gonococcal cervicitis: a role for biofilm in pathogenesis. J Infect Dis. 198(12):1856-61, 2008. Srikhanta, Y.N., Dowideit, S.J., Edwards, J.L., Falsetta, M.L., Wu, H-J., Harrison, O.B., Fox, K.L., Seib, K.L., Maguire, T.L., Wang, A.H.-J., Maiden, M.C., Grimmond, S.M., Apicella M.A. and Jennings, M.P. Phasevarions mediate random switching of gene expression in pathogenic Neisseria. PLoS Pathogens 5(4):e1000400. PMID: 19390608; PMCID: PMC2667262, April 2009. |
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| Department/Program Affiliations |
| Microbiology |
| Biosciences |
| Immunology |
| Molecular and Cellular Biology |
| MSTP |