Resistance to nitric oxide in Mycobacterium avium complex and its implication in pathogenesis

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Mycobacterium avium complex (MAC) is an opportunistic pathogen.
• Nitric oxide (NO) is a key mediator of immune responses against intracellular pathogens.
• The role of NO in controlling MAC infection is not fully understood.

Purpose of the Study:

• To investigate the susceptibility of different MAC strains to nitric oxide (NO).
• To examine the effects of NO on macrophage phagocytosis and superoxide anion generation.
• To understand the mechanisms underlying MAC pathogenesis related to NO resistance.

Main Methods:

• In vitro susceptibility testing of MAC strains (M. avium Mino, M. intracellulare 31F093T, KUMS 9007) to NO.
• Assessment of NO generation by gamma interferon (IFN-gamma)-stimulated rat alveolar macrophages (M phi).
• Evaluation of NO's impact on M phi phagocytosis and superoxide anion (O2-) production.

Main Results:

• M. avium Mino growth was suppressed by IFN-gamma-stimulated M phi-derived NO, unlike M. intracellulare strains.
• M. avium Mino was more susceptible to chemically generated NO than M. intracellulare strains.
• High NO levels suppressed M phi phagocytosis and O2- generation, particularly after infection with NO-resistant M. intracellulare 31F093T.

Conclusions:

• MAC strain-dependent variation exists in susceptibility to macrophage-derived NO.
• NO resistance in MAC strains can lead to impaired macrophage function, facilitating bacterial spread.
• NO resistance is a potential factor contributing to the pathogenicity of MAC.