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Role of iron in the pathogenesis of Mycobacterium avium infection in mice
A M Dhople1, M A Ibanez, T C Poirier
1Department of Biological Sciences, Florida Institute of Technology, Melbourne 32901, USA.
Abstract:
Mycobacterial infections are of serious concern to HIV-infected patients, and take a heavy toll of such patients. Mycobacterium avium is the most common opportunistic bacterial infection in patients with AIDS. The overload of iron in serum has been implicated in the pathogenicity of a number of bacterial infections. Since iron storage in cells such as macrophages is increased in AIDS, the role of iron as a possible factor in the pathogenesis of M. avium infection was examined. Supplementing iron to normal laboratory chow resulted in accelerated M. avium infection in mice inoculated earlier with the same organism. The bacterial loads in liver, spleen and lungs were approximately 12-fold higher in mice receiving iron supplementation compared with control groups. This is attributed to an increased percentage saturation of iron in the sera of the mice, thus making more iron available for the replication of bacteria. The addition of beef fat to the diet, together with high iron supplementation, further enhanced the infection. Using smaller inocula, mice receiving chow supplemented with high iron and fat developed disseminated M. avium infection faster than control mice. The results provide strong evidence that iron may play a major role in the pathogenesis of M. avium infection.
Insights
Iron overload accelerates Mycobacterium avium infection in patients with AIDS. Supplementing iron in mice diets significantly increased bacterial loads, highlighting iron
Area of Science:
- Infectious Diseases
- Immunology
- Nutritional Science
Background:
- Mycobacterial infections, particularly Mycobacterium avium, are a significant threat to individuals with HIV/AIDS.
- Elevated serum iron levels are suspected to contribute to the pathogenicity of various bacterial infections.
- Increased iron storage in macrophages is observed in AIDS patients, suggesting a potential role for iron in disease progression.
Purpose of the Study:
- To investigate the role of iron in the pathogenesis of Mycobacterium avium infection in the context of AIDS.
Main Methods:
- Mice were inoculated with Mycobacterium avium.
- Dietary iron supplementation was administered to assess its impact on infection.
- Bacterial loads in organs (liver, spleen, lungs) were quantified.
- The effect of combined iron and fat supplementation was also evaluated.
Main Results:
- Iron supplementation led to an approximate 12-fold increase in bacterial loads in the liver, spleen, and lungs of infected mice.
- This increase correlated with higher serum iron saturation, providing more iron for bacterial replication.
- Combined high iron and fat supplementation further enhanced M. avium infection, leading to faster disseminated disease.
Conclusions:
- Dietary iron plays a critical role in the pathogenesis of Mycobacterium avium infection.
- Iron availability significantly influences bacterial replication and disease progression in this model.
- Findings suggest that iron management could be a potential therapeutic target for M. avium infections in immunocompromised individuals.