The antimicrobial wasp Polybia-MP1 peptide selectively kills bacterial cells!

The Polybia-MP1 peptide (IDWKKLLDAAKQIL-NH₂) obtained from the venom of the social wasp Polybia paulista is highly selective of bacterial cells.

In 2005, Sauza et al. isolated two novel peptides from the venom of the social wasp Polybia paulista. The research group utilized a combination of electrospray-mass spectrometry (ESI-MS) and Edman degradation chemistry-based sequencing for the characterization of these peptides as Polybia-MPI: IDWKKLLDAAKQIL-NH₂ (1654.09 Da) and Polybia-CP: ILGTILGLLKSL-NH₂ (1239.73 Da).

Sauza et al. characterized Polybia-MPI as a mast cell lytic peptide causing no hemolysis to rat erythrocytes but is chemotaxis for polymorphonucleated leukocytes and shows a potent antimicrobial action both against Gram-positive and Gram-negative bacteria.

The researchers identified Polybia-CP as a chemotactic peptide for polymorphonucleated leukocytes with antimicrobial action against Gram-positive bacteria, but causing no hemolysis to rat erythrocytes and no mast cell degranulation activity at physiological concentrations.

The MP1 peptide exhibits broad-spectrum bacterial activity and inhibits cancer cells. Specifically, it is an antimicrobial and chemotactic peptide for polymorphonucleated leukocytes, the most abundant circulating blood leukocytes, andis also a potent antimicrobial peptide against Gram-positive bacteria B. subtilis and S. aureus and Gram-negative bacteria E. coli ATCC 25922 and P. aeruginosa ATCC 15422. The peptide has a low cytotoxicity to normal, non-cancerous cells and preferentially interacts with anionic lipid vesicles over zwitterionic ones.

This antimicrobial peptide has a decreased activity in membranes containing cholesterol. In vivo, blood biochemical parameters after mice injection suggest that the peptide induces acute renal failure, hemolysis, rhabdomyolysis, and hepatic necrosis. The death of mice appears to be due to acute renal failure resulting from rhabdomyolysis (muscle breakdown) and intravascular hemolysis. The peptide is more toxic to cancer cell lines than primary non-cancer cells (human primary lymphocytes). The peptide induces necrosis and pore-like activity on Jurkat cells with several bilayer compositions. The peptide also has a membranolytic activity on human glioblastoma multiform cells (brain tumor cells), leading to cell necrosis.

Polybia-MP1 selectively inhibits the proliferation of prostate and bladder cancer cell lines and the associated endothelial cells and is effective against multidrug-resistant leukemic cells. The peptide shows anticancer activity when tested on sarcoma xenograft tumors in vivo.

Alvares et al., in 2017, investigated the effects of Polybia MP1 on membrane lipids, specifically, the interaction with negatively charged phosphatidylserine (PS) monolayers in comparison to those formed by the zwitterionic lipid, phosphatidylcholine (PC). The study highlighted the incorporation of MP1 into PS membranes, regulating the membrane's physical properties.

The study's results indicated that the MP1 peptide affects artificial membranes containing the hopanoid diplopterol (DP) or cholesterol (CHO) differently. DP-containing membranes are less protected against leakage and peptide entry. Diplopterol, also known as hopan-22-ol, is a lipid natural product belonging to the family of triterpenoids known as the hopanoids. Diplopterol performs similar functions involving membrane fluidity tuning.

In addition to electrostatic interactions, neutral lipids such as sterols and hopanoids appear important factors in MP1 selectivity. The observed results suggest that membranes containing DP do not rupture after peptide delivery but become permeable, leading to cell death.

In 2021, Alvares et al. reported how peptide-membrane affinity, peptide-lytic activity, and peptide effects on membrane properties are affected by DP compared to CHO. The research group used a simple membrane composition to study binary mixtures with CHO or DP, a phospholipid, and pure phospholipid membranes. The phospholipid POPC (2-oleoyl-1-palmitoyl-sn-glycero-3- phosphocholine) was chosen as a model for fluid biological membranes because it is a widely studied lipid that forms liquid-disordered membranes.

The study results showed that MP1 distinguishes DP-containing membranes from those with CHO by inducing pore formation. However, translocation of the peptide did not lead to vesicle rupture, suggesting that the presence of DP in the cell membrane is not as effective as CHO for protecting bacteria from the action of this peptide.

Bio-Synthesis has extensive expertise in synthesizing these peptide types, including a list of other antimicrobial peptides.

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