원문정보
초록
영어
Tuberculosis (TB) has been a major world-wide cause of death for centuries. One-third of the world’s population is infected with Mycobacterium tuberculosis (M.tb), the etiologic agent of TB. The development of potent new anti-TB drugs is urgently needed. The major M.tb surface lipoglycans, mannose-capped Lipoarabinomannan (ManLAM) had immunosuppressive effects during M.tb infection. In this study, aptamer ZXL1 which specifically bound to ManLAM from the virulent strain M.tb H37Rv was screened out by Systematic Evolution of Ligands by EXponential enrichment (SELEX). The binding affinity of ZXL1 to ManLAM was measured as 8.907X10-8 M of quilibrium dissociation constant (Kd) value by surface plasmon resonance (SPR) analysis. We found that aptamer ZXL1 prevented the ManLAM-induced immunosuppressive effects on DCs and inhibited M. tb entry into macrophages. More importantly, we found that single injection of aptamer ZXL1 significantly prolonged the survival rate of infected mice, and prevent the infected rhesus monkeys from weight loss. The Bacterial numbers were significantly lower in the lungs and spleens in ZXL1-treated groups. These results suggest that aptamer ZXL1 can be used as antimycobacterial agent or as TB vaccine adjuvent.