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Mycobacterium tuberculosis promotes genomic instability in macrophages

BACKGROUND

Mycobacterium tuberculosis is an intracellular pathogen, which may either block cellular defensive mechanisms and survive inside the host cell or induce cell death. Several studies are still exploring the mechanisms involved in these processes.

OBJECTIVES

To evaluate the genomic instability of M. tuberculosis-infected macrophages and compare it with that of uninfected macrophages.

METHODS

We analysed the possible variations in the genomic instability of Mycobacterium-infected macrophages using the DNA breakage detection fluorescence in situ hybridisation (DBD-FISH) technique with a whole human genome DNA probe.

FINDINGS

Quantitative image analyses showed a significant increase in DNA damage in infected macrophages as compared with uninfected cells. DNA breaks were localised in nuclear membrane blebs, as confirmed with DNA fragmentation assay. Furthermore, a significant increase in micronuclei and nuclear abnormalities were observed in infected macrophages versus uninfected cells.

MAIN CONCLUSIONS

Genomic instability occurs during mycobacterial infection and these data may be seminal for future research on host cell DNA damage in M. tuberculosis infection.

Key words:
Mycobacterium tuberculosis; alkaline-labile sites; DNA breakage detection fluorescence in situ hybridisation (DBD-FISH)


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