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Demonstration of lipooligosaccharide immunotype and capsule as virulence factors for Neisseria meningitidis using an infant mouse intranasal infection model
Affiliation:1. T Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA;2. Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA;3. Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA;4. Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA;1. Xi''an Medical University, Xi''an, Shaanxi 710021, China;2. Department of Cardiovascular Medicine, Shaanxi Provincial People''s Hospital, Xi''an, 710068, China;3. Gansu Provincial People''s Hospital, Lanzhou, 730000, China;4. Department of Nursing, Xi''an Jiaotong University School of Medicine, Xi''an, Shaanxi 710061, China;5. The First Affiliated Hospital of Xi''an Jiaotong University School of Medicine, Xi''an, Shaanxi 710061, China;1. Institute of Biomedicine and Translational Medicine, Department of Pharmacology, University of Tartu, 50411 Tartu, Estonia;2. Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, Finland;3. Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia
Abstract:Using an infant mouse intranasal infection model, we have compared the virulence of 17 epidemiologically related isolates of Neisseria meningitidis associated with an outbreak of meningococcal disease in Gloucestershire, UK, and one germane isolate. The isolates were all of serotype 15 subtype P1:7, 16 and were identical by restriction fragment length polymorphism analysis, but differed in either (i) whether they were isolated from a case or a carrier, (ii) the presence or absence of group B capsule, or (iii) their lipooligosaccharide (LOS) immunotype. The results indicate that capsule is a major virulence determinant and is required for colonization and hence for invasion. In addition, the LOS L3,7,9 immunotype, when compared to the L1,8,10 immunotype, is a secondary virulence factor which enhances colonization of nasal passages and invasion of the blood stream by both case and carrier isolates. Two case isolates which were unusual in possessing the L1,8,10 immunotype, established invasive infection, but this was associated with a switch to the L3,7,9 immunotype. The results confirm that LOS is a virulence factor for N. meningitidis and that immunotype L3,7,9 is associated with invasive disease.
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