The role of APTX4870 peptide in reducing cellular inflammatory responses by inhibiting Mycobacterium tuberculosis-derived mycolic acid-induced cytotoxicity

APTX4870肽通过抑制结核分枝杆菌衍生的霉菌酸诱导的细胞毒性在降低细胞炎症反应中的作用

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作者:Xue Lin, Wei Jia, Gangning Feng, Yajing Su, Yuting Kang, Chen Zhang, Wenmiao Liu, Zhidong Lu, Di Xue

Abstract

Tuberculosis is a serious zoonotic disease caused by Mycobacterium tuberculosis (M.tb) and the M.tb complex. Mycolic acid is an extracellular carbohydrate polymer produced, secreted, and accumulated outside the cells of various Mycobacterium tuberculosis strains. Mycolic acid produced by Mycobacterium plays an important role in infection. However, there have been few reports on drugs that inhibit mycolic acid-induced cytotoxicity. The purpose of this study was to investigate the role of the panned peptide in Mycobacterium-derived mycolic acid (M.tb-MA)-induced cell injury. The heptapeptide (APTX4870) was isolated from various phage libraries using phage display (Ph.D-7, Ph.D-12, and Ph.D-C7C). The efficacy of APTX4870 against mycolic acid was demonstrated by evaluating clinical samples and conducting in vitro and Vivo. APTX4870 inhibited apoptosis, increased autophagy to decrease inflammation, and reduced M.tb-MA-induced lung damage. These findings suggest that this heptapeptide, which selectively targets M.tb-MA, might be exploited as a potential novel M.tb therapeutic treatment.

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