Difference in virulence of Mycobacterium avium isolates sharing indistinguishable DNA fingerprint determined in murine model of lung infection

• Published in: PloS one Vol. 6; no. 6; p. e21673
• Main Authors: Amaral, Eduardo Pinheiro, Kipnis, Thereza Liberman, de Carvalho, Eulógio Carlos Queiróz, da Silva, Wilmar Dias, Leão, Sylvia Cardoso, Lasunskaia, Elena B
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.06.2011; Public Library of Science (PLoS)
• Subjects: Analysis; Animal models; Animals; Bacteria; Biological properties; Biology; Bone marrow; Cells, Cultured; Chronic infection; Clinical isolates; Cloning; Deoxyribonucleic acid; Disease susceptibility; DNA; DNA Fingerprinting - methods; DNA, Bacterial - genetics; Epidemiology; Female; Fingerprints; Gene expression; Genotype & phenotype; Genotyping; Health aspects; Health risks; Histopathology; Hogs; House mouse; Immunity; Immunocompromised hosts; Immunology; Infections; Interferon; Laboratories; Lung diseases; Lung Diseases - microbiology; Lungs; Lymph nodes; Male; Mathematical models; Medical research; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium; Mycobacterium avium; Mycobacterium avium - genetics; Mycobacterium avium - pathogenicity; Mycobacterium tuberculosis; Pathogens; Polymerase Chain Reaction; Similarity; Strains (organisms); Tuberculosis; Virulence; Virulence (Microbiology); Virulence - genetics; Virulence - physiology; Brazil; Rio de Janeiro Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0021673

Opportunistic Mycobacterium avium typically causes disease in immunocompromised patients and in some groups of apparently healthy individuals. The high virulence of some bacterial lineages increases the disease risk. High-resolution molecular genotyping studies of M. avium clinical isolates demonstrated that some genotype patterns were more prevalent than others, suggesting that close genetic relatedness of these successful isolates sharing a similar genotype could determine similar biological properties associated with high virulence. In this study, we aimed to compare the virulence and pathogenic properties of two epidemiologically unrelated M. avium isolates sharing an indistinguishable DNA fingerprint in a well-characterized model of pulmonary infection in mice, resistant or susceptible to mycobacteria. The mice, C57BL/6 wild- type or IFN-gamma gene disrupted (GKO), respectively, were intratracheally infected with two isolates, H27 (human blood isolate) and P104 (pig lymph node isolate), and the lungs were examined for bacterial loads, histopathology and cytokine gene expression. The obtained data demonstrated significant differences in the virulence properties of these strains. Although the H27 strain grew significantly faster than P104 in the early stage of infection, this bacterium induced protective immunity that started to reduce bacterial numbers in the wild-type mice, whereas the P104 strain established a chronic infection. In the GKO mice, both strains were capable of causing a chronic infection, associated with higher bacterial burdens and severe lung pathology, in a similar manner. The results demonstrated that the studied isolates differed in the pathogenic properties although were indistinguishable by actually widely used genotyping techniques demonstrating that the genotype similarity does not predict similarity in virulence of M. avium isolates.