A new bioinspired peptide on defensin from C. annuum fruits: Antimicrobial activity, mechanisms of action and therapeutical potential

Gabriel Bonan Taveira; Érica de Oliveira Mello; Thatiana Lopes Biá Ventura Simão; Milena Bellei Cherene; André de Oliveira Carvalho; Michelle Frazão Muzitano; Elena Lassounskaia; Saulo Pireda; Emílio de Castro Miguel; Luis Guilherme Mansor Basso; Maura Da Cunha; Olney Vieira da Motta; Valdirene Moreira Gomes

doi:10.1016/j.bbagen.2022.130218

A new bioinspired peptide on defensin from C. annuum fruits: Antimicrobial activity, mechanisms of action and therapeutical potential

Biochim Biophys Acta Gen Subj. 2022 Nov;1866(11):130218. doi: 10.1016/j.bbagen.2022.130218. Epub 2022 Jul 26.

Authors

Affiliations

¹ Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil. Electronic address: gabrielbtaveira@yahoo.com.br.
² Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil.
³ Laboratório de produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Pólo Novo Cavaleiro-IMMT, Macaé, RJ 27933-378, Brazil; Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil.
⁴ Laboratório de produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Pólo Novo Cavaleiro-IMMT, Macaé, RJ 27933-378, Brazil.
⁵ Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil.
⁶ Laboratório de Biologia Celular e Tecidual, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil.
⁷ Departamento de Engenharia Metalúrgica, Universidade Federal do Ceará, Campus do Pici, Fortaleza, CE 600020-181, Brazil.
⁸ Laboratório de Ciências Físicas, Centro de Ciência e Tecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil.
⁹ Laboratório de Sanidade Animal, Centro de Ciências e Tecnologias Agropecuárias, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil.
¹⁰ Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil. Electronic address: valmg@uenf.br.

PMID: 35905923
DOI: 10.1016/j.bbagen.2022.130218

Abstract

Background: Antimicrobial peptides, natural or synthetic, appear as promising molecules for antimicrobial therapy because of their both broad antimicrobial activity and mechanism of action. Herein, we determine the anti-Candida and antimycobacterial activities, mechanism of action on yeasts, and cytotoxicity on mammalian cells in the presence of the bioinspired peptide CaDef2.1_G27-K44.

Methods: CaDef2.1_G27-K44 was designed to attain the following criteria: high positive net charge; low molecular weight (<3000 Da); Boman index ≤2.5; and total hydrophobic ratio ≥ 40%. The mechanism of action was studied by growth inhibition, plasma membrane permeabilization, ROS induction, mitochondrial functionality, and metacaspase activity assays. The cytotoxicity on macrophages, monocytes, and erythrocytes were also determined.

Results: CaDef2.1_G27-K44 showed inhibitory activity against Candida spp. with MIC₁₀₀ values ranging from 25 to 50 μM and the standard and clinical isolate of Mycobacterium tuberculosis with MIC₅₀ of 33.2 and 55.4 μM, respectively. We demonstrate that CaDef2.1_G27-K44 is active against yeasts at different salt concentrations, induced morphological alterations, caused membrane permeabilization, increased ROS, causes loss of mitochondrial functionality, and activation of metacaspases. CaDef2.1_G27-K44 has low cytotoxicity against mammalian cells.

Conclusions: The results obtained showed that CaDef2.1_G27-K44 has great antimicrobial activity against Candida spp. and M. tuberculosis with low toxicity to host cells. For Candida spp., the treatment with CaDef2.1_G27-K44 induces a process of regulated cell death with apoptosis-like features.

General significance: We show a new AMP bioinspired with physicochemical characteristics important for selectivity and antimicrobial activity, which is a promising candidate for drug development, mainly to control Candida infections.

Keywords: Anti-Candida activity; Antimicrobial peptide; Antimycobacterial; Apoptosis-like; Membrane permeabilization; ROS increase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents
Anti-Infective Agents*
Candida
Defensins
Fruit*
Mammals
Peptides
Reactive Oxygen Species

Substances

Anti-Bacterial Agents
Anti-Infective Agents
Defensins
Peptides
Reactive Oxygen Species