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. 2023 Jan;55(1):113-124.
doi: 10.1007/s00726-022-03209-6. Epub 2023 Jan 6.

Inspiration from cruzioseptin-1: membranolytic analogue with improved antibacterial properties

Sebastián Bermúdez-Puga  1 , Giovanna Morán-Marcillo  1 , Nina Espinosa de Los Monteros-Silva  1 , Renato E Naranjo  2 , Fernanda Toscano  3 , Karla Vizuete  4 , Marbel Torres Arias  3 , José R Almeida  1 , Carolina Proaño-Bolaños  5
Affiliations

Inspiration from cruzioseptin-1: membranolytic analogue with improved antibacterial properties

Sebastián Bermúdez-Puga et al. Amino Acids. 2023 Jan.

Abstract

Peptide engineering has gained attraction as a source of new cationicity-enhanced analogues with high potential for the design of next-generation antibiotics. In this context, cruzioseptin-1 (CZS-1), a peptide identified from Cruziohyla calcarifer, is recognized for its antimicrobial potency. However, this amidated-peptide is moderately hemolytic. In order to reduce toxicity and increase antimicrobial potency, 3 peptide analogues based on cruzioseptin-1 were designed and evaluated. [K4K15]CZS-1, an analogue with increased cationicity and reduced hydrophobicity, showed antibacterial, antifungal and antiproliferative properties. In addition, [K4K15]CZS-1 is less hemolytic than CZS-1. The in silico and scanning electron microscopy analysis reveal that [K4K15]CZS-1 induces a membranolytic effect on bacteria. Overall, these results confirm the potential of CZS-1 as source of inspiration for design new selective antimicrobial analogues useful for development of new therapeutic agents.

Keywords: Antimicrobial peptides; Cruzioseptin; Membranolytic effect; Rational design.

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