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Association of plasmids and virulence of Mycobacterium avium complex
P R Gangadharam1, V K Perumal, J T Crawford
1Mycobacteriology Research Laboratories, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Abstract:
Mycobacterium avium complex strain LR25, which carries 3 plasmids, was shown to be of high virulence in beige mice as judged by high mortality and a progressive increase in organisms in the spleen and lungs determined by counting the number of colony-forming units. Strain LR163, a "cured" derivative of LR25 that lacks all 3 plasmids, was of low virulence as judged by these criteria. The relative virulence of the strains was confirmed by studies of oxygen metabolite (superoxide anion and hydrogen peroxide) release from resident and BCG-activated mouse peritoneal macrophages. In contrast to loss of virulence, no significant change was seen in drug susceptibility.
Insights
Mycobacterium avium complex virulence is linked to plasmids. Removing plasmids from strain LR25 significantly reduced its virulence in mice, demonstrating plasmid-encoded virulence factors.
Area of Science:
- Microbiology and Immunology
- Infectious Diseases
Background:
- Mycobacterium avium complex (MAC) is an opportunistic pathogen.
- The genetic basis of MAC virulence is not fully understood.
- Plasmids are extrachromosomal DNA elements found in bacteria.
Purpose of the Study:
- To investigate the role of plasmids in the virulence of Mycobacterium avium complex strain LR25.
- To determine if plasmid loss affects the pathogenicity of MAC.
Main Methods:
- Comparison of virulence between MAC strain LR25 (with plasmids) and strain LR163 (cured, plasmid-deficient) in beige mice.
- Quantification of bacterial load in spleen and lungs using colony-forming units (CFUs).
- Assessment of macrophage oxygen metabolite release (superoxide anion, hydrogen peroxide) upon exposure to MAC strains.
Main Results:
- MAC strain LR25 exhibited high virulence, causing high mortality and increased bacterial burden in spleen and lungs.
- The plasmid-cured strain LR163 showed significantly reduced virulence by the same criteria.
- Macrophage studies corroborated the difference in virulence, with strain LR25 eliciting a different response compared to LR163.
- Drug susceptibility remained unchanged between the virulent and avirulent strains.
Conclusions:
- Plasmids carried by Mycobacterium avium complex strain LR25 contribute significantly to its high virulence in a mouse model.
- Loss of these plasmids attenuates MAC virulence without affecting drug susceptibility.
- Plasmids encode factors crucial for MAC pathogenesis.