Virulence traits of serogroup C meningococcus and isogenic mutant, defective in surface-exposed sialic acid, in a murine model of meningitis.

Colicchio, Roberta; Pagliuca, Chiara; Ricci, Susanna; Scaglione, Elena; Grandgirard, Denis; Masouris, Ilias; Farina, Fabrizio; Pagliarulo, Caterina; Mantova, Giuseppe; Paragliola, Laura; Leib, Stephen; Koedel, Uwe; Pozzi, Gianni; Alifano, Pietro; Salvatore, Paola (2019). Virulence traits of serogroup C meningococcus and isogenic mutant, defective in surface-exposed sialic acid, in a murine model of meningitis. Infection and immunity, 87(4) American Society for Microbiology 10.1128/IAI.00688-18

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In serogroup C the () gene codes for an UDP--acetylglucosamine 2-epimerase that catalyzes the conversion of UDP--acetyl-α-D-glucosamine into -acetyl-D-mannosamine and UDP in the first step in sialic acid biosynthesis. This enzyme is required for the biosynthesis of the (α2→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 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 (LD) of the wild type strain 93/4286 was about four orders of magnitude lower than that of the 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 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 , indicating high tropism of meningococci exposing sialic acids toward this brain structure and a specific involvement of the in the mouse model of meningococcal meningitis.

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