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.
키워드
tuberculosisManLAMaptamer
저자
Qin Pan [ State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology,Wuhan University School of Medicine, Donghu Road 165#, Wuhan 430071, Hubei Province, China ]
Qilong Wang [ State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology,Wuhan University School of Medicine, Donghu Road 165#, Wuhan 430071, Hubei Province, China ]
Fengling Luo [ State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology,Wuhan University School of Medicine, Donghu Road 165#, Wuhan 430071, Hubei Province, China ]
Min Li [ State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology,Wuhan University School of Medicine, Donghu Road 165#, Wuhan 430071, Hubei Province, China ]
Xianru Xia Dongdong Shi [ State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology,Wuhan University School of Medicine, Donghu Road 165#, Wuhan 430071, Hubei Province, China ]
Xiao-Lian Zhang [ State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology,Wuhan University School of Medicine, Donghu Road 165#, Wuhan 430071, Hubei Province, China ]
Corresponding author
본 학회는 화학, 생화학, 분자생물학, 미생물학, 식품공학, 의학, 약학, 유전공학 및 생물공학, 환경 및 기타 공업 등 전 분야의 탄수화물관련 이론과 기술을 연구 발전시키고 산학협동을 통해 이를 보급하여 국내 관련 산업의 발전 및 국민생활의 과학화에 기여하고자 하며, 이러한 목표와 비젼의 실현을 위해 회원들이 적극적인 참여와 활동을 전개하고자 한다.