das Neves Rogerio Coutinho, Trentini Monalisa Martins, de Castro e Silva Juliana, Simon Karina Smidt, Bocca Anamelia Lorenzetti, Silva Luciano Paulino, Mortari Marcia Renata, Kipnis Andre, Junqueira-Kipnis Ana Paula
Department of Microbiology, Immunology, Parasitology and Pathology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Brazil.
Laboratório de Toxinologia. Campus Darcy Ribeiro, Instituto de Ciências Biológicas, Departamento de Ciências Fisiológicas, University of Brasilia, Brasília, Brazil.
PLoS One. 2016 Mar 1;11(3):e0149729. doi: 10.1371/journal.pone.0149729. eCollection 2016.
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.
脓肿分枝杆菌马西利亚亚种是一种快速生长的分枝杆菌（RGM），在人类传染病中变得越来越重要，具有毒性和致病性，并且对几种可能阻碍其清除的抗菌药物具有固有抗性。因此，迫切需要鉴定新的药物以改善当前的治疗方法或降低诱导耐药性的风险。黄蜂毒液主要由负责这种毒液中大部分生物活性的肽组成。在这里，一种来自新热带黄蜂多形多刺蚁的新型肽Polydim-I被作为一种抗分枝杆菌剂进行了研究。Polydim-I引起细胞壁破坏，并且对哺乳动物细胞表现出无细胞毒性。用Polydim-I处理感染不同脓肿分枝杆菌马西利亚亚种菌株的巨噬细胞，可使细菌载量降低40%至50%。此外，用Polydim-I处理静脉内感染脓肿分枝杆菌马西利亚亚种的高度易感小鼠，可使肺、脾和肝中的细菌载量降低0.8至1个对数。总之，这是第一项显示黄蜂毒液衍生肽在治疗分枝杆菌感染方面具有治疗潜力的研究。Polydim-I作用于脓肿分枝杆菌马西利亚亚种细胞壁，并在体外和体内使细菌载量降低40%-90%。所呈现的结果鼓励进一步研究将Polydim-I用作脓肿分枝杆菌马西利亚亚种治疗的成分之一。
