Memariani Hamed, Memariani Mojtaba
Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
Probiotics Antimicrob Proteins. 2025 Jun;17(3):1217-1235. doi: 10.1007/s12602-025-10455-z. Epub 2025 Jan 20.
Notwithstanding the indefatigable endeavors to develop effective anti-mycobacterial therapies, mycobacterial infections still present a tough problem for medicine today. The problem is further complicated by the disquieting surge of drug-resistant mycobacterial pathogens, which considerably narrows the existing therapeutic options. Thus, there is a genuine need to discover novel anti-mycobacterial drugs. Animal venoms are considered a treasure trove of structurally variable and biologically active peptides, which may hold promise for therapeutic applications. Over the past two decades, abundant evidence has been amassed regarding anti-mycobacterial effects of various peptides derived from the venoms of honeybees, wasps, scorpions, pseudoscorpions, cone snails, and snakes. This review intends to consolidate the state-of-the-art knowledge on the anti-mycobacterial peptides of animal venoms and to sketch potentially fruitful directions for future investigations. The available data indicate that micromolar concentrations of particular venom-derived peptides can effectively inhibit the in vitro growth of Mycobacterium tuberculosis and non-tuberculous mycobacteria. The proposed mechanisms of action of venom-derived peptides include reduced activity of plasma membrane ATPase, depolarization of the cell membrane, disruption of the cell wall, and increased generation of reactive oxygen species. Interestingly, administering certain peptides (≤ 2 mg/kg body weight) through daily intraperitoneal injections to mice for 8 consecutive days resulted in lower levels of mycobacterial infections and inflammation, hitting two targets with one arrow. Indubitably, such peptides can usher in new possibilities for the prevention and treatment of recalcitrant mycobacterial infections.
尽管人们不懈努力研发有效的抗分枝杆菌疗法，但分枝杆菌感染如今仍是医学上的一个难题。耐药分枝杆菌病原体令人不安地激增，使这一问题更加复杂，因为这大大缩小了现有的治疗选择范围。因此，确实需要发现新型抗分枝杆菌药物。动物毒液被认为是结构多样且具有生物活性的肽的宝库，可能具有治疗应用前景。在过去二十年中，已经积累了大量证据，证明来自蜜蜂、黄蜂、蝎子、拟蝎、芋螺和蛇毒液的各种肽具有抗分枝杆菌作用。本综述旨在整合关于动物毒液抗分枝杆菌肽的最新知识，并勾勒未来研究可能富有成果的方向。现有数据表明，特定毒液衍生肽的微摩尔浓度可有效抑制结核分枝杆菌和非结核分枝杆菌的体外生长。毒液衍生肽的拟作用机制包括降低质膜ATP酶活性、使细胞膜去极化、破坏细胞壁以及增加活性氧的产生。有趣的是，连续8天每天给小鼠腹腔注射某些肽（≤2mg/kg体重），可降低分枝杆菌感染和炎症水平，一箭双雕。毫无疑问，此类肽可为顽固性分枝杆菌感染的预防和治疗带来新的可能性。
