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Exposure to ethanol up-regulates the expression of Mycobacterium avium complex proteins associated with bacterial
L E Bermudez1, L S Young, J Martinelli
1Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center, San Francisco.
Abstract:
Mycobacterium avium complex (MAC) organisms are the most common bacterial cause of disseminated infection in patients with AIDS. MAC, facultative intracellular bacteria, invade and multiply within macrophages. Treatment of MAC-infected macrophages with ethanol (10-100 micrograms/dL) is associated with increased intracellular multiplication of MAC. To investigate whether this enhanced growth is due to a stress-related response induced by nonlethal concentrations of ethanol, strain 101 (serovar 1) was exposed to ethanol, and the regulation of the expression of proteins was examined. Exposure of MAC to ethanol (range, 10-100 micrograms/dL) was associated with up-regulation of the expression of a number of bacterial proteins, some of which (65 and 33 kDa) interfered with macrophage functions, such as production of superoxide anion and killing of Staphylococcus aureus. Thus, exposure of MAC to small concentrations of ethanol may induce a stress-related response with consequent increase in the synthesis of proteins possibly associated with its ability to survive within macrophages.
Insights
Ethanol exposure increases Mycobacterium avium complex (MAC) growth in macrophages. This stress response up-regulates bacterial proteins that impair macrophage functions, aiding MAC survival.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Mycobacterium avium complex (MAC) causes disseminated infections in AIDS patients.
- MAC are facultative intracellular bacteria that infect macrophages.
Purpose of the Study:
- Investigate if ethanol induces a stress response in MAC, enhancing intracellular growth.
- Examine the regulation of protein expression in ethanol-exposed MAC.
Main Methods:
- Exposed MAC strain 101 to ethanol (10-100 micrograms/dL).
- Analyzed bacterial protein expression changes.
- Assessed impact on macrophage functions (superoxide anion production, Staphylococcus aureus killing).
Main Results:
- Ethanol exposure up-regulated expression of several MAC proteins.
- Specific proteins (65 and 33 kDa) interfered with macrophage functions.
- Increased intracellular MAC multiplication observed.
Conclusions:
- Non-lethal ethanol concentrations induce a stress response in MAC.
- This response increases synthesis of proteins potentially enhancing macrophage survival.
- Ethanol may contribute to MAC pathogenesis in immunocompromised individuals.