Sialic acids of both the capsule and the sialylated lipooligosaccharide of Neisseria meningitis serogroup B are prerequisites for virulence of meningococci in the infant rat

TLDR: It is concluded that in the infant rat model of meningococcal infection both forms of sialic acid on the bacterial cell surface are indispensable for systemic survival.

Abstract: We investigated the contribution of the polysialic acid capsule and of terminal lipooligosaccharide (LOS) sialylation to the pathogenicity of Neisseria meningitidis in vivo using a set of defined isogenic mutants of the N. meningitidis strain B 1940 deficient in either capsule synthesis or LOS sialylation. Furthermore a spontaneous capsule-deficient variant was investigated, which was capable of switching on the capsule synthesis at a frequency of 3 x 10(-3) in vitro. Infection of infant rats with the wild-type strain revealed a high potential to cause bacteremia. This potential was attenuated in the capsule-phase variable mutant (LOS sialylation+). However, using a mutant irreversibly deficient in capsule synthesis, but expressing a sialylated LOS, bacteremia could only be achieved using 10(6) times higher numbers of bacteria when compared to the wild-type. The unencapsulated bacteria were located extracellularly upon examination of blood smears, suggesting that defense mechanisms, i.e. phagocytosis, directed against unencapsulated meningococci were exhausted using very high infecting doses. Interestingly, when infant rats were infected with encapsulated meningococci which were unable to sialylate the LOS, bacteremia could never be achieved, even with an infective dose as high as 10(8) colony forming units (CFU). Despite the presence of capsular polysaccharide this mutant was phagocytosed by peritoneal phagocytes, as was the unencapsulated, LOS-sialylated mutant, suggesting that the inability to cause bacteremia was due to a higher susceptibility to the action of the complement system, which is virtually unsaturable. We conclude that in the infant rat model of meningococcal infection both forms of sialic acid on the bacterial cell surface are indispensable for systemic survival.