Antimycobacterial Activity of a New Peptide Polydim-I Isolated from Neotropical Social Wasp Polybia dimorpha

Mycobacterium abscessus subsp. massiliense, a rapidly growing mycobacteria (RGM) that is becoming increasingly important among human infectious diseases, is virulent and pathogenic and presents intrinsic resistance to several antimicrobial drugs that might hamper their elimination. Therefore, the identification of new drugs to improve the current treatment or lower the risk of inducing resistance is urgently needed. Wasp venom primarily comprises peptides that are responsible for most of the biological activities in this poison. Here, a novel peptide Polydim-I, from Polybia dimorpha Neotropical wasp, was explored as an antimycobacterial agent. Polydim-I provoked cell wall disruption and exhibited non-cytotoxicity towards mammalian cells. Polydim-I treatment of macrophages infected with different M. abscessus subsp. massiliense strains reduced 40 to 50% of the bacterial load. Additionally, the Polydim-I treatment of highly susceptible mice intravenously infected with M. abscessus subsp. massiliense induced 0.8 to 1 log reduction of the bacterial load in the lungs, spleen, and liver. In conclusion, this is the first study to show the therapeutic potential of a peptide derived from wasp venom in treating mycobacteria infections. Polydim-I acts on the M. abscessus subsp. massiliense cell wall and reduce 40–90% of the bacterial load both in vitro and in vivo. The presented results encourage further studies on the use of Polydim-I as one of the components for M. abscessus subsp. massiliense treatment.

脓肿分枝杆菌马氏亚种（Mycobacterium abscessus subsp. massiliense）是一类快速生长分枝杆菌（rapidly growing mycobacteria, RGM），其在人类传染病领域的受关注度与日俱增。该菌兼具毒力与致病性，且对多种抗菌药物存在固有耐药性，这为临床清除该菌带来了阻碍。因此，亟需开发新型药物以优化现有治疗方案、降低耐药诱导风险。
蜂毒（wasp venom）的核心组分为多肽，此类多肽是该毒液绝大多数生物学活性的介导物质。本研究针对源自新热带区多形胡蜂（Polybia dimorpha）的新型多肽Polydim-I，探究其作为抗分枝杆菌制剂的应用潜力。实验结果显示，Polydim-I可诱导该菌细胞壁破裂，且对哺乳动物细胞无细胞毒性。用Polydim-I处理感染不同脓肿分枝杆菌马氏亚种菌株的巨噬细胞，可使细菌载量降低40%~50%。此外，对经静脉感染脓肿分枝杆菌马氏亚种的高度易感小鼠施以Polydim-I治疗，可使其肺、脾、肝组织的细菌载量降低0.8~1 log值。
综上，本研究首次证实了源自蜂毒的多肽在治疗分枝杆菌感染中的治疗潜力。Polydim-I通过作用于脓肿分枝杆菌马氏亚种的细胞壁，在体外（in vitro）与体内（in vivo）实验中均可使细菌载量降低40%~90%。本研究所得结果为后续将Polydim-I作为脓肿分枝杆菌马氏亚种治疗方案的组分之一开展进一步研究提供了支撑。