The role of the mycobacterial DNA-binding protein 1 (MDP1) from Mycobacterium bovis BCG in host cell interaction

BMC Microbiology

Astrid Lewin¹  Elisabeth Kamal¹  Ralph Kunisch¹ 

[1] Division 16 Mycology/Parasitology/Intracellular Pathogens, Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany

关键词: Host interaction;    Virulence;    Granuloma;    Latency;    Histone-like protein;    DNA-binding protein;    MDP1;    Mycobacterial DNA-binding protein 1;    Tuberculosis;    Mycobacterium;   

Others  :  1221799
DOI  :  10.1186/1471-2180-12-165

 received in 2012-04-05, accepted in 2012-07-27,  发布年份 2012

【 摘 要 】

Background

Mycobacterium tuberculosis differs from most pathogens in its ability to multiply inside monocytes and to persist during long periods of time within granuloma in a status of latency. A class of proteins called mycobacterial histone-like proteins has been associated with regulation of replication and latency, but their precise role in the infection process has yet to be uncovered. Our study aimed at defining the impact of the histone-like protein MDP1 from M. bovis BCG (mycobacterial DNA-binding protein 1, corresponding to Rv2986c from M. tuberculosis) on early steps of infection.

Results

Previously, a BCG (Bacillus Calmette Guérin) strain had been generated by antisense-technique exhibiting reduced MDP1 expression. This strain was now used to analyse the impact of reduced amount of MDP1 on the interaction with human blood monocytes, macrophage lines and PBMC (peripheral blood mononuclear cells). MDP1 was revealed to be required for growth at acidic pH and for intracellular replication in human blood monocytes. Down-regulation of MDP1 resulted in reduced secretion of the cytokine IL-1β by infected human PBMC. In addition, a reduction of MDP1 expression had a major impact on the formation of fused multi-nucleated macrophages. In monocyte preparations from human blood as well as in human and mouse macrophage cell lines, both the percentage of multi-nucleated cells and the number of nuclei per cell were much enhanced when the monocytes were infected with BCG expressing less MDP1.

Conclusion

MDP1 from M. bovis BCG affects the growth at acidic pH and the intracellular replication in human monocytes. It furthermore affects cytokine secretion by host cells, and the formation of fused multi-nucleated macrophages. Our results suggest an important role of MDP1 in persistent infection.

【 授权许可】

   
2012 Kunisch et al.; licensee BioMed Central Ltd.

【 图 表 】

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