Mouse models of infection for Neisseria meningitidis B,2b and Haemophilus influenzae type b diseases

Abstract

A disseminated and fatal infection was established in C57BL mice, injected intraperitoneally with either Neisseria meningitidis B,2b or Haemophilus influenzae type b bacteria plus enhancement factors. The effects of mucin, hemoglobin, and iron dextran as enhancement of bacterial infectivity in mice were evaluated individually and in combination. A mixture of mucin and hemoglobin was most effective in enhancing the virulence of the pathogens. Inbred mouse lines were more susceptible than outbred ones. Relative virulence of a number of bacterial strains was also compared in one selected mouse line. Neisseria meningitidis B,2b and Haemophilus influenzae type b strains were more virulent than non-B,2b and nontypable strains. Finally, the course of bacteremia for the two infections in mice was followed by quantitative blood cultures. The animals succumbed to the generalized condition within 72 h. In the case of Neisseria meningitidis B,2b, 10 organisms with 4% mucin and 1.6% hemoglobin were sufficient to kill 50% of the animals. For Haemophilus influenzae type b, 300 bacteria with 5% mucin and 2% hemoglobin were necessary to obtain similar effects.

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.…”

“…However, the large doses of organisms required and the speed with which the animals die suggest that mortality is the consequence of toxicity rather than a true infection (31). In contrast, when mice are supplemented with an accessible iron source, such as hTF or iron dextran, consistently high mortality rates are achieved with doses of bacteria several orders of magnitude lower (5,6,22,44). 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 contrast, when mice are supplemented with an accessible iron source, such as hTF or iron dextran, consistently high mortality rates are achieved with doses of bacteria several orders of magnitude lower (5,6,22,44). 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).…”

Two-Component Systems in Haemophilus influenzae : a Regulatory Role for ArcA in Serum Resistance

“…The bacteria were resuspended to a density of 0.36 absorbance unit at 600 nm, corresponding to 7.2 ϫ 10 7 CFU/ml, in a saline solution, and 10-fold dilutions were prepared. Each dilution was verified by colony counting and was injected intraperitoneally (0.5 ml per mouse) as a 1:1 mixture with enhancement medium (2% mucin and 2% bovine hemoglobin) (7). Groups of five mice were inoculated with each bacterial dose.…”

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).…”