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Aptamer inhibits Mycobacterium tuberculosis (H37Rv) invasion of macrophage

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Abstract

There is an urgent need to develop new anti-tuberculosis drugs due to the rising tendency in tuberculosis (TB) around the world. It is known that Mycobacterium tuberculosis (M. tuberculosis) generally infects mammalian host via aerosol route. The pathogenic process has been fully studied that it can initially invade alveolar macrophage, then established stable residence within those phagocytic cells, suggesting that one of the possible ways to prevent this pathogen is to inhibit its invasion and growth in the macrophage. Aptamers from SELEX (Systematic Evolution of Ligands by Exponential Enrichment) have been used to rival virulent M. tuberculosis (H37Rv) in our previous work, and the materials to which aptamers bound were proved to be some outer membrane proteins of H37Rv. In the present study, the interaction between M. tuberculosis and macrophage in the presence of aptamers was investigated in more details. The results suggested that the selective aptamers significantly inhibited H37Rv invasion of macrophage in vitro, and the effect correspond to the binding affinity of these aptamers to H37Rv. The values of equilibrium dissociation constant (Kd) was calculated by flow cytometry, all in the nanomolar range, showed much higher affinity to H37Rv than M. bovis Bacillus Guerin (BCG). Moreover, the aptamer-treated H37Rv can stimulate IFN-γ, IL-15 and IL-17 secretion of macrophages compared with H37Rv (no treated). In summary, our data indicated that the NK2 aptamer not only acted as anti-tuberculosis agent by inhibiting virulent M. tuberculosis (H37Rv) invasion of macrophage, but also might be used as molecular probe for exploring the interaction between the outer membrane of M. tuberculosis and macrophage.

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Authors and Affiliations

  1. The Faculty of Life Sciences, Hubei University, 368 Youyi Road, Wuchang, 430062, Wuhan, China

    Fan Chen

  2. Department of Immunology, State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, 430071, China

    XiaoLian Zhang, Shengwu Liu & Junyan Liu

  3. Wuhan Tuberculosis Dispensary, 28 Baofeng Road, Qiaokou, Wuhan, 430030, China

    Jing Zhou

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  1. Fan Chen
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  2. XiaoLian Zhang
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  3. Jing Zhou
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  4. Shengwu Liu
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  5. Junyan Liu
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Correspondence to Fan Chen.

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Chen, F., Zhang, X., Zhou, J. et al. Aptamer inhibits Mycobacterium tuberculosis (H37Rv) invasion of macrophage. Mol Biol Rep 39, 2157–2162 (2012). https://doi.org/10.1007/s11033-011-0963-3

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  • DOI: https://doi.org/10.1007/s11033-011-0963-3

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