Experimental meningococcal infection in neonatal animals: models for mucosal invasiveness

Abstract

A more complete understanding of meningococcal disease has been hampered by lack of an appropriate animal model. We subjected 5-day-old guinea pigs, rats, and mice to intranasal challenge with meningococci and we measured rates of bacteremia as a marker of mucosal invasion. After a single intranasal instillation of 10(7) serotype 2 meningococci, positive blood cultures were found in 0% of guinea pigs, 16% of rats, and 39% of mice, and so mice were used for further studies. Death occurred in 4% of mice and was associated with a purulent leptomeningitis and ventriculitis. Forty percent of mice had nasopharyngeal colonization which increased to 65% with repeated injections. Carrier strains were avirulent, a nonserotype 2 disease strain had low invasiveness, and serotype 2 strains were most virulent. Iron dextran increased rates of bacteremia after challenge with serotype 2 strains. Adult animals were not susceptible to bacteremia after intranasal challenge. The neonatal mouse model fulfills most of the criteria for an appropriate experimental model of meningococcal disease.

Neisseria meningitidis Expressing Transferrin Binding Proteins of Actinobacillus pleuropneumoniae Can Utilize Porcine Transferrin for Growth

“…Animal models of meningococcal infections which are capable of causing bacteremia and meningitis have been developed mostly with mice, and they require the injection of an iron source such as iron salts or hTF into the animals in order to sustain bacteremia and generate high mortality rates (5,6,22,30,40,44). The generation of an N. meningitidis mutant capable of growth with pTF as its sole iron source introduces the possibility of generating an animal model of meningococcal infection in the pig, which would not require injection of an iron source.…”

“…At these doses, the survival and pathogenicity of N. meningitidis strains in mice are clearly dependent on the levels of an accessible iron source (5,6,22,44). In an attempt to mimic the route of entry of N. meningitidis more realistically, infant mice have been successfully infected via the nasal route, although, as with previous models, a supplement of hTF or iron dextran is necessary (30,40). If N. meningitidis could be engineered to utilize iron from TF from a suitable animal host, an animal model which more closely mimics the course of the human infection might be developed.…”

Growth of Neisseria gonorrhoeae in the Female Mouse Genital Tract Does Not Require the Gonococcal Transferrin or Hemoglobin Receptors and May Be Enhanced by Commensal Lactobacilli

“…It has long been known that experimental meningococcal septicemia and nasopharyngeal colonization of mice can be enhanced by the coadministration of iron dextran (24,50,51), human transferrin, human lactoferrin (52), or hemoglobin (7). Similarly, growth of N. gonorrhoeae in the peritoneums of adult mice and dissemination into the bloodstream required the administration of hemoglobin (13).…”

Animal models for pathogenic Neisseria species

“…Various animal models including monkeys, rabbits, guinea pigs, mice, and chicken embryos have been used in the study of different aspects of meningococcal pathogenesis (18, 22,34,44). Of these species, the laboratory mouse is probably one of the more versatile animals in terms of methods for inducing infection, because we can select inbred lines with well-characterized immunologic features.…”

“…Disease-associated strains generally induced a fatal infection in mice after the injection of relatively few microorganisms (<10 colony-forming units), whereas less virulent or carrier strains had a 50% lethal dose of >104 colony-forming units (26). Salit (44) described a mouse model in which intranasal challenge was used to test tHe invasive potential of disease-and carrier-associated strains. Approximately 40% of 2-to 5-day-old mice became bacteremic by 48 to 72 h after intranasal inoculation with virulent meningococci.…”