A new bioinspired peptide on defensin from C. annuum fruits: Antimicrobial activity, mechanisms of action and therapeutical potential.
Biochim Biophys Acta Gen Subj
; 1866(11): 130218, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35905923
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 CaDef2.1G27-K44.METHODS:
CaDef2.1G27-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:
CaDef2.1G27-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 CaDef2.1G27-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. CaDef2.1G27-K44 has low cytotoxicity against mammalian cells.CONCLUSIONS:
The results obtained showed that CaDef2.1G27-K44 has great antimicrobial activity against Candida spp. and M. tuberculosis with low toxicity to host cells. For Candida spp., the treatment with CaDef2.1G27-K44 induces a process of regulated cell death with apoptosis-like features. GENERALSIGNIFICANCE:
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.Palavras-chave
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Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Terapias_biologicas
Assunto principal:
Frutas
/
Anti-Infecciosos
Idioma:
En
Revista:
Biochim Biophys Acta Gen Subj
Ano de publicação:
2022
Tipo de documento:
Article