Antimicrobial and antibiofilm activity of the EeCentrocin 1 derived peptide EC1-17KV via membrane disruption

Abstract

Background: The antibiotic resistance and biofilm formation of pathogenic microbes exacerbate the difficulties of anti-infection therapy in the clinic. The structural modification of antimicrobial peptides (AMP) is an effective strategy to develop novel anti-infective agents. Method: Seventeen amino acids (AA) in the longer chain of EeCentrocin 1 (from the edible sea-urchin Echinus esculentus) were truncated and underwent further modification. To produce lead peptides with low toxicity and high efficacy, the antimicrobial activity or cytotoxicity of peptides was evaluated against various multidrug-resistant bacteria/fungi or mammalian cells in vivo/ in vitro. In addition, the stability and modes of action of the lead peptide were investigated. Findings: EC1-17KV displayed potent activity and an expanded antimicrobial spectrum, especially against drug-resistant gram-negative bacteria and fungi, attributable to its enhanced amphiphilicity and net charge. In addition, it exhibits bactericidal/fungicidal activity and effectively increased the animal survival rate and mitigated the histopathological damage induced by multidrug-resistant P. aeruginosa or C. albicans in infected mice or G. mellonella. Moreover, EC1-17KV had a poor ability to induce resistance in bacteria and fungi and exhibited desirable high-salt/high-temperature tolerance properties. In bacteria, EC1-17KV promoted divalent cation release to damage bacterial membrane integrity. In fungi, it changed C. albicans membrane fluidity to increase membrane permeabilization or reduced hyphal formation to suppress biofilm formation. Interpretation: EC1-17KV is a promising lead peptide for the development of antimicrobial agents against antibiotic resistant bacteria and fungi.

Novel Hybrid Peptide Cathelicidin 2 (1-13)-Thymopentin (TP5) and Its Derived Peptides with Effective Antibacterial, Antibiofilm, and Anti-Adhesion Activities

“…Though biofilms originate from planktonic bacteria, they differ in their properties. Therefore, the antibiofilm mechanisms of AMPs include the following aspects: direct damage to the bacterial cell membrane [20][21][22]; interference of the QS system [23][24][25]; reduction of extracellular polymeric substances (EPS) accumulation [26]; and inhibition of stringent response [27].…”

Antifungal In Vitro Activity of Pilosulin- and Ponericin-Like Peptides from the Giant Ant Dinoponera quadriceps and Synergistic Effects with Antimycotic Drugs

“…In fact, venom and venom-peptides from ants and insects commonly cause cell lysis, like hemolysis, and tissue damage that are intrinsic biological properties that contribute to the overall envenomation symptoms [48,49]. Indeed, a number of AMPs are active due to their membranolytic mechanism of action [50,51], therefore these peptides are invariably and potentially cytotoxic whether they are not selective to the pathogen targets. Thus, thinking about the potential use of AMPs from venom, two immediate practical concepts could be envisioned and solutions carried out: One is the reduction of the potential cytotoxicity by amino acid substitution in a peptide-design program [52,53].…”

“…The action on pathogen membranes can be accompanied of either membrane lysis and cytoplasmic extravasation or intracellular penetration and interaction with intracellular targets, among other particular mechanisms of action. Several reports have detailed the action of AMPs on the cell membranes of microorganisms [18,50,51,61,62] and pilosulin-and ponericin-like peptides from D. quadriceps could be added to these groups of membranolytic peptides. Thus, since the cell membrane of yeasts is mostly made up of ergosterol, it was important to investigate the influence of soluble ergosterol in the culture medium, on the activity of peptides, as the primary approach.…”

Alternative Therapeutic Interventions: Antimicrobial Peptides and Small Molecules to Treat Microbial Keratitis

“…Several peptides designed and synthesized have been tested against various bacteria and fungus both in vitro and in vivo . EC1-17KV, synthetic peptides based on the antimicrobial peptide EeCentrocin 1 from Echinus esculentus , was efficient in killing MDR P. aeruginosa and exhibited multiple modes of action, including direct membrane disruption and inhibitory effects on cell adhesion and biofilm formation ( Ma et al, 2020 ). Another novel short α-helical hybrid peptide inspired by natural α-helical AMPs, PA-13, showed remarkable broad-spectrum antibacterial activity, especially against P. aeruginosa with no toxicity to mammalian cells.…”