Tachyplesin and CyLoP-1 as efficient anti-mycobacterial peptides: A novel finding

Abstract

Mycobacterium tuberculosis is an etiological agent of tuberculosis (TB) known to be a highly contagious disease and is the major cause of mortality from a single infectious agent worldwide. Emergence of multi-drug resistant and extremely drug resistant strains of M. tuberculosis has made TB management extremely challenging eliciting the urgent need for alternative therapeutics. Peptide based therapeutic strategies are an emerging area that can be employed as a prospective alternative to the currently existing therapeutic regime for TB treatment. Here, we are reporting the anti-mycobacterial activity of two peptides, Tachyplesin and CyLoP-1, derived from marine horseshoe crab and snake toxin respectively, with potent anti-mycobacterial activity against various mycobacterium species. Both the peptides exhibit appreciable antimicrobial and anti-biofilm activities against mycobacterium species with minimum cytotoxicity towards macrophage cells. They are also effective in eliminating mycobacterium cells from infected macrophage cells. Tachyplesin acts on mycobacterium cells in a lytic manner with outer membrane disruption confirmed by propidium iodide uptake with slight membrane depolarization and reactive oxygen species (ROS) production. CyLoP-1, on the other hand, does not rupture the mycobacterium cells even at high concentrations. It seems to follow intracellular pathway of killing mycobacterium cells by production of more ROS and membrane depolarization. Both the peptides do not lead to apoptotic way of mycobacterium cell death. These results suggest an effective peptide-based antimicrobial strategy for development of future anti-TB therapeutics.

Keywords: Anti-mycobacterial peptides; Membrane active peptides; Membrane depolarization; Mycobacterium smegmatis; Reactive oxygen species; Tuberculosis.