Experimental meningococcal infection in mice: a model for mucosal invasion

Abstract

A nmore complete understanding of meningococcal disease has been hampered by the lack of an appropriate animal model. Previous models have utilized injections of meningococci, which precludes the study of nasopharyngeal colonization and invasion. We have developed a model for meningococcal disease in which litters of 5-day-old mice are challenged intranasally with 107 viable meningococci. Bacteremia is monitored by jugular venous blood cultures, and cerebrospinal fluid is sanlpled by cisternal punctures. Human diseaseassociated and carrier strains were compared; nasopharyngeal colonization was similar for these bacteria, but the case-associated strains were much more frequently invasive and caused bacteremia. Twenty-one percent of bacteremic animals had meningitis. There was an age-related susceptibility to infection which correlated inversely with the levels of serum complement. Prein'ection of iron dextran increased the number of animals which were bacteremic, the concentration of bacteria in blood, and nasopharyngeal colonization. Noncapsular variants of virulent meningococci did not colonize nasopharyngeal tissue in vivo, and they were not invasive. This neonatal mouse model mimics meningococcal disease as seen in humans and may be useful in studying the initial events in the pathogenesis of meningococcal disease.

Attenuated virulence of Streptococcus agalactiae deficient in D‐alanyl‐lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells

“…Group B streptococci is the leading cause of meningitis in human newborns. In the neonatal rat model, development of GBS meningitis is correlated with the magnitude and duration of bacteraemia (Ferrieri et al, 1980), an observation which is also true for other bacterial pathogens responsible for childhood meningitis (Bortolussi et al, 1978;Salit and Tomalty, 1986;Berche, 1995). We observed that in a mouse i.v.…”

Invasion of brain microvascular endothelial cells by group B streptococci

“…Inadequate understanding of the basic pathogenic mechanisms by which GBS penetrate the CNS contributes to the high morbidity and mortality associated with this infection. In the neonatal rat model, development of GBS meningitis is correlated to the magnitude and duration of bacteremia (17), an observation which holds for other bacterial agents of childhood meningitis (5,43). The studies described herein demonstrate for the first time that GBS are capable of invading human BMEC, the single-cell layer which comprises the blood-brain barrier.…”

Clonal diversity of Neisseria meningitidis from a population of asymptomatic carriers

“…Bacterial capsules have been implicated in virulence, and in the mouse model, comparisons of virulence of isogenic meningococcal strains that differ only in production of polysaccharide have demonstrated the importance of the capsule for invasiveness (20). Spontaneous revertants from nonencapsulated variants can be obtained at significant frequencies both in vitro and in vivo (20,26). However, the mechanism(s) that regulates the synthesis of capsular polysaccharides in N. meningitidis is unknown.…”