title: Function of ssDNA aptamer and aptamer pool against Mycobacterium tuberculosis             in a mouse model.
abstract: Novel antibacterial agents against Mycobacterium tuberculosis (MTB) are crucial due to the high infection and mortality rates associated with the disease. Our previous study confirmed that aptamers from a whole bacterium obtained by the Systematic Evolution of Ligands by Exponential Enrichment method specifically bound to the MTB virulent strain (H37Rv). In the present study, the function of aptamers against MTB in a mouse model was further determined. It was demonstrated that the NK2 aptamer has marked inhibitory effects on the adhesion/invasion of H37Rv to macrophages in vitro and stimulates intracellular IFN-γ production in CD4+ T-cells. The aptamer pool exhibited the strongest inhibitory effect on H37Rv adhesion/invasion to CD8+ T-cells in vitro compared with all aptamers-treated and control groups. Histopathological examination of lung biopsy specimens revealed a correlation between aptamer presence and lower pulmonary alveoli fusion, swelling and more prominent air spaces. Acid-fast staining of biopsy specimens from the lungs of the mice demonstrated parallel treatment effects. Results of the present study indicate that the 10th pool aptamers and NK2 may play an active role against H37Rv, however, the effect was different in vivo and in vitro. The treatment effect of 10th pool aptamers was found to be better in comparison to NK2 in vivo. Additional target sites involved in pathogenicity of H37Rv were also revealed and the NK2 binding site and aptamers, including the 10th pool aptamers, may antagonize these sites. Further studies are required to screen for other valuable aptamers which may be used as therapeutic drugs in combination with NK2.
authors.affiliation: Faculty of Life Sciences, Hubei University, Wuchang, Wuhan 430062,                     P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Yong-Hao
authors.initials: YH
authors.lastname: Huang
authors.forename: Feng-Ying
authors.initials: FY
authors.lastname: Huang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Fang
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Xiong
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Lin
authors.forename: Guang-Hong
authors.initials: GH
authors.lastname: Tan
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000382:microbiology; D004277:DNA, Single-Stranded / Q000737:chemistry*; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000472:pathogenicity; D052156:SELEX Aptamer Technique
chemical_list: D052157:Aptamers, Nucleotide; D004277:DNA, Single-Stranded; D007371:Interferon-gamma