PMID:22192908

Citation	Guo, S, Xue, R, Li, Y, Wang, SM, Ren, L and Xu, JJ (2012) The CFP10/ESAT6 complex of Mycobacterium tuberculosis may function as a regulator of macrophage cell death at different stages of tuberculosis infection. Med. Hypotheses 78:389-92
Abstract	Tuberculosis is a human disease caused by infection with Mycobacterium tuberculosis. M. tuberculosis (Mtb) is a facultative intracellular pathogen. The alveolar macrophages provide a critical niche for the intracellular pathogen. It has been shown that virulent strains mycobacteria (Mtb-H37Rv, Mycobacterium bovis) induce less apoptosis in host macrophage than avirulent mycobacteria strains (Bacillus Calmette-Guérin, H37Ra). Comparative genomics analysis has revealed that the region of difference (RD1) of M. tuberculosis is absent from all strains of Bacillus Calmette-Guérin (BCG). On the contrary, it presents in all virulent strains of M. tuberculosis and M. bovis. The culture filtrate protein 10 (CFP10) and early secretory antigenic target protein 6 (ESAT6) are encoded by RD1 genes Rv3874 and Rv3875, respectively. Recent studies indicated that the CFP10 and ESAT6 played an important role in M. tuberculosis virulence. It has been shown that incorporation of the RD1 region into BCG to restore the expression of CFP10 and ESAT6 leads to increasing the virulence and immunogenicity of bacterium. On the contrary, deletion of the genes encoding CFP10 and ESAT6 from the virulent M. bovis strain results in attenuation of virulence. Meanwhile, several studies showed that CFP10 and ESAT6 could inhibit and/or promote the production of tumor necrosis factor α (TNF-α) from macrophages. Furthermore, TNF-α can induce apoptosis and necrosis of infected macrophages in tuberculosis. Considering above results, we hypothesize that the CFP10 and ESAT6 may be involved in the virulence of Mycobacterium through modulating macrophage cell death.
Links	PubMed Online version:10.1016/j.mehy.2011.11.022
Keywords	Antigens, Bacterial/genetics; Antigens, Bacterial/metabolism; Apoptosis/physiology; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Humans; Macrophages/metabolism; Macrophages/physiology; Models, Biological; Multiprotein Complexes/genetics; Multiprotein Complexes/metabolism; Mycobacterium tuberculosis/metabolism; Mycobacterium tuberculosis/pathogenicity; Tuberculosis/physiopathology; Tumor Necrosis Factor-alpha/metabolism; Virulence
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
9MYCO:B2CXA0	NOT	GO:0009405: pathogenesis	ECO:0000315:		P			complete CACAO 11278

References

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