Aptamer from whole-bacterium SELEX as new therapeutic reagent against virulent Mycobacterium tuberculosis.
Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB. Because of the global health problems of TB, the development of potent new anti-TB drugs without cross-resistance with known antimycobacterial agents is urgently needed. In this study, we have applied a Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process to identify a single aptamer (NK2) that binds to virulent strain M. tuberculosis (H37Rv) with high affinity and specificity. We have found that this aptamer improves CD4(+)T cells to produce IFN-gamma after binding to H37Rv. The different component between H37Rv and BCG was identified as some membrane protein. Moreover, the survival rates of mice challenged with i.v. H37Rv have been prolonged after treatment with single injection of aptamer NK2. The bacterial numbers were significantly lower in the spleen of mice treated with aptamer NK2. The histopathological examination of lung biopsy specimens showed lesser pulmonary alveolar fusion and swelling in the presence of the aptamer. These results suggest that aptamer NK2 has inhibitory effects on M. tuberculosis and can be used as antimycobacterial agent.
Chen
Fan
F
Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, State Key Laboratory of Virology, Wuhan University School of Medicine, Donghu Road 165#, Wuhan 430071, Hubei Province, China.
Zhou
Jing
J
Luo
Fengling
F
Mohammed
Al-Bayati
AB
Zhang
Xiao-Lian
XL
D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D052156:SELEX Aptamer Technique / Q000379:methods; D015996:Survival Rate; D013816:Thermodynamics; D014376:Tuberculosis / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D014774:Virulence
D000995:Antitubercular Agents; D052157:Aptamers, Nucleotide; D017252:CD3 Complex; D007371:Interferon-gamma