Antichagasic effect of hemocyanin derived from antimicrobial peptides of penaeus monodon shrimp

Exp Parasitol. 2020 Aug:215:107930. doi: 10.1016/j.exppara.2020.107930. Epub 2020 May 25.

Abstract

Trypanosoma cruzi, the etiological agent of Chagas disease, is responsible for the infection of millions of people worldwide and it is a public health problem, without an effective cure. Four fragments with antimicrobial potential from the hemocyanin of Penaeus monodon shrimp were identified using a computer software AMPA. The present study aimed to evaluate the antichagasic effect of these four peptides (Hmc364-382, Hmc666-678, Hmc185-197 and Hmc476-498). The peptides were tested against the epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi Y strain (benznidazole-resistant strain) and cytotoxicity in mammalian cells was evaluated against LLC-MK2 lineage cells. Two fragments (Hmc364-382, Hmc666-678) showed activity against the epimastigote and trypomastigote forms and their selectivity index (SI) was calculated. The Hmc364-382 peptide was considered the most promising (SI > 50) one and it was used for further studies, using flow cytometry analyses with specific molecular probes and scanning electron microscopy (SEM). Hmc364-382 was able to induce cell death in T. cruzi through necrosis, observed by loss of membrane integrity in flow cytometry analyses and pore formation in SEM. Overall, Hmc364-382 open perspectives to the development of new antichagasic agents.

Keywords: Antimicrobial peptides; Chagas disease; Hemocyanin; Penaeus monodon; Shrimp; Trypanosoma cruzi.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / chemistry*
  • Antimicrobial Cationic Peptides / toxicity
  • Cell Line / drug effects
  • Cell Survival / drug effects
  • Chagas Disease / drug therapy
  • Flow Cytometry
  • Hemocyanins / pharmacology*
  • Hemocyanins / toxicity
  • Inhibitory Concentration 50
  • Macaca mulatta
  • Microscopy, Electron, Scanning
  • Penaeidae / chemistry*
  • Time Factors
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / growth & development
  • Trypanosoma cruzi / ultrastructure

Substances

  • Antimicrobial Cationic Peptides
  • Hemocyanins