1. Virulence traits of a serogroup C Meningococcus and isogenic cssA mutant, defective in surface-exposed sialic acid, in a murine model of meningitis
- Author
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Laura Paragliola, Chiara Pagliuca, Pietro Alifano, Fabrizio Farina, Gianni Pozzi, Ilias Masouris, Roberta Colicchio, Susanna Ricci, Paola Salvatore, Giuseppe Mantova, Caterina Pagliarulo, Uwe Koedel, Stephen L. Leib, Elena Scaglione, Denis Grandgirard, Colicchio, R., Pagliuca, C., Ricci, S., Scaglione, E., Grandgirard, D., Masouris, I., Farina, F., Pagliarulo, C., Mantova, G., Paragliol, L., Leib, S. L., Koedel, U., Pozzi, G., Alifano, P., Salvatorea, P., Colicchio, Roberta, Pagliuca, Chiara, Ricci, Susanna, Scaglione, Elena, Grandgirard, Deni, Masouris, Ilia, Farina, Fabrizio, Pagliarulo, Caterina, Mantova, Giuseppe, Laura, Paragliola, Leib Stephen, L., Koedel, Uwe, Pozzi, Gianni, Alifano, Pietro, and Salvatore, Paola
- Subjects
0301 basic medicine ,Mutant ,Neisseria meningitidis, Serogroup C ,Neisseria meningitidis ,medicine.disease_cause ,corpus callosum ,Gene Knockout Techniques ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Capsule ,Mice, Inbred BALB C ,Virulence ,LOS ,Gene Knockout Technique ,Meningoencephalitis ,Brain ,meningitis mouse models ,meningoencephalitis ,Bacterial Infections ,Infectious Diseases ,sialic acid ,Meningitis mouse model ,Female ,Meningitis ,Human ,capsule ,Corpus callosum ,Immunology ,Bacterial Protein ,Biology ,Carbohydrate Epimerase ,Meningitis, Meningococcal ,Microbiology ,03 medical and health sciences ,Bacterial Proteins ,medicine ,Neisseria meningitidi ,Animals ,Humans ,Tropism ,Animal ,Wild type ,medicine.disease ,Sialic acid ,N-Acetylneuraminic Acid ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Parasitology ,Carbohydrate Epimerases ,030217 neurology & neurosurgery ,Meningoencephaliti - Abstract
In serogroup C Neisseria meningitidis, the cssA (siaA) gene codes for an UDP-N-acetylglucosamine 2-epimerase that catalyzes the conversion of UDP-N-acetyl-alpha-D-glucosamine into N-acetyl-D-mannosamine and UDP in the first step in sialic acid biosynthesis. This enzyme is required for the biosynthesis of the (alpha 2 -> 9)-linked polysialic acid capsule and for lipooligosaccharide (LOS) sialylation. In this study, we have used a reference serogroup C meningococcal strain and an isogenic cssA knockout mutant to investigate the pathogenetic role of surface-exposed sialic acids in a model of meningitis based on intracisternal inoculation of BALB/c mice. Results confirmed the key role of surface-exposed sialic acids in meningococcal pathogenesis. The 50% lethal dose (LD50) of the wild-type strain 93/4286 was about four orders of magnitude lower than that of the cssA mutant. Compared to the wild-type strain, the ability of this mutant to replicate in brain and spread systemically was severely impaired. Evaluation of brain damage evidenced a significant reduction in cerebral hemorrhages in mice infected with the mutant in comparison with the levels in those challenged with the wild-type strain. Histological analysis showed the typical features of bacterial meningitis, including inflammatory cells in the subarachnoid, perivascular, and ventricular spaces especially in animals infected with the wild type. Noticeably, 80% of mice infected with the wild-type strain presented with massive bacterial localization and accompanying inflammatory infiltrate in the corpus callosum, indicating high tropism of meningococci exposing sialic acids toward this brain structure and a specific involvement of the corpus callosum in the mouse model of meningococcal meningitis.
- Published
- 2019