Rv2820c of Beijing/W strains enhances Mycobacterium tuberculosis survival in human macrophages

Abstract

The ability to survive in human macrophages is a hallmark of the virulence of Mycobacterium tuberculosis. Although the intracellular parasitism is apparent, the molecular determinants behind are still largely unknown. The truncated Rv2820c of the Beijing/W strains of Mycobacterium tuberculosis was previously shown to enhance the survival of Mycobacterium smegmatis in the human macrophages. The enhanced intracellular survival, however, was not observed in the recombinant harboring the intact Rv2820c of the non-Beijing/W strains. In the current investigation, the role of the truncated Rv2820c in M. tuberculosis was examined using a ‘gain-of-function’ manner. The truncated Rv2820c was transformed into non-Beijing/W strains of M. tuberculosis and the resulting recombinants were used to infect the monocytic cell line THP-1. The ex vivo infection showed that the non-Beijing/W M. tuberculosis recombinants survived significantly better than the vector controls after ten days of infection (P < 0.05; independent samples t-test, two-tailed). Similar levels of interleukin-6, interleukin-10, and tumor necrosis factor-alpha were secreted from the macrophages infected with those non-Beijing/W recombinants. This study showed that the Rv2820c of the Beijing/W strains is capable of enhancing the M. tuberculosis survival in the human macrophages, but is unlikely to evoke a different profile of cytokine secretion from the infected macrophages. It suggests that the truncated Rv2820c may be another Beijing/W-specific virulence determinant.