Abstract
BackgroundOpportunistic 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.Methods and FindingsIn 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.Conclusions/SignificanceThe 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.
Highlights
Infection with opportunistic Mycobacterium avium subsp. hominissuis is a significant health problem among HIV-infected populations [1], children with genetic deficiencies in IFN-c and IL-12 production or function [2], in individuals with a prior history of lung pathology and among subsets of apparently healthy people, such as thin elderly women [3,4]
Growth of two M. avium isolates in 7H9 Middlebrook broth and in bone marrow-derived macrophages obtained from C57BL/6 mice
In order to evaluate virulence-associated properties of two pathogenic M. avium isolates, H27 and P104, with previously determined genotypes, we first studied the intrinsic capacity of these bacteria to grow in the specific mycobacterial medium, 7H9 Middlebrook broth, as well as measured the bacterial capacity to intracellular growth in murine macrophages
Summary
Infection with opportunistic Mycobacterium avium subsp. hominissuis is a significant health problem among HIV-infected populations [1], children with genetic deficiencies in IFN-c and IL-12 production or function [2], in individuals with a prior history of lung pathology and among subsets of apparently healthy people, such as thin elderly women [3,4]. In another study performed in Brazil, a large cluster of M. avium isolates obtained from pigs and human patients, exhibiting indistinguishable DNA fingerprinting pattern as determined by IS1245-based RFLP and PCR-restriction enzyme analysis of hsp (PRA-hsp65) methods, was identified as a result of genotyping of 108 individual isolates [12]. These data suggest that the close genetic relatedness of these successful isolates sharing a similar genotype could determine similar biological properties associated with increased virulence of these strains, but this issue has never been tested in direct experiments. Highresolution 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
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