New Frontiers in Fighting Mycobacterial Infections: Venom-Derived Peptides.

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.