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Iron-controlled infection with Neisseria meningitidis in mice
Abstract:
An iron-controlled infection was obtained after the intraperitoneal infection of Neisseria meningitidis strain M1011 into normal mice. The infection progressed rapidly but then disappeared in concert with the disappearance of plasma transferrin iron. Parenteral iron dextran enhanced and prolonged the infection in mice at dosages above 15 mg of Fe per kg. Studies on the distribution of iron dextran within the physiological iron pools and the importance of timing with the iron dextran addition indicated that high serum iron, available early during infection, was necessary to promote infection. High levels of iron in the reticuloendothelial system did not stimulate infection. A working hypothesis to explain the roles of iron in infection was developed: N. meningitidis obtains iron for growth from the transferrin pool, and iron dextran maintains transferrin iron levels during infection.
Insights
Iron dextran supplementation significantly enhances Neisseria meningitidis infections in mice by maintaining vital transferrin iron levels. Early administration of iron is crucial for promoting bacterial growth and prolonging illness.
Area of Science:
- Microbiology
- Immunology
- Nutritional Science
Background:
- Neisseria meningitidis infections are a significant public health concern.
- The role of iron availability in bacterial pathogenesis is well-established.
- Understanding iron acquisition mechanisms is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the impact of exogenous iron administration on the course of Neisseria meningitidis infection in a murine model.
- To elucidate the specific iron pools utilized by N. meningitidis during infection.
- To develop a hypothesis regarding iron's role in meningococcal pathogenesis.
Main Methods:
- Induction of iron-controlled infection using Neisseria meningitidis strain M1011 in normal mice.
- Administration of parenteral iron dextran at varying dosages and timings.
- Monitoring of infection progression and correlation with plasma transferrin iron levels.
- Analysis of iron distribution within physiological iron pools.
Main Results:
- Parenteral iron dextran (above 15 mg Fe/kg) enhanced and prolonged N. meningitidis infections.
- Early availability of high serum iron levels was critical for infection enhancement.
- Iron accumulation in the reticuloendothelial system did not promote infection.
- Infection severity correlated inversely with plasma transferrin iron availability.
Conclusions:
- Neisseria meningitidis utilizes plasma transferrin-bound iron for growth during infection.
- Exogenous iron administration, specifically iron dextran, can exacerbate meningococcal infections by maintaining transferrin iron levels.
- Targeting iron acquisition pathways may represent a viable therapeutic approach against meningococcal disease.