A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional Characterization

Antimicrobial peptides (AMPs) are excellent candidates to fight multi-resistant pathogens worldwide and are considered promising bio-preservatives to control microbial spoilage through food processing. To date, designing de novo AMPs with high therapeutic indexes, low-cost synthesis, high resistance...

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Main Authors: Bruna Agrillo, Yolande T. R. Proroga, Marta Gogliettino, Marco Balestrieri, Rosarita Tatè, Luigi Nicolais, Gianna Palmieri
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/18/6952
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author Bruna Agrillo
Yolande T. R. Proroga
Marta Gogliettino
Marco Balestrieri
Rosarita Tatè
Luigi Nicolais
Gianna Palmieri
author_facet Bruna Agrillo
Yolande T. R. Proroga
Marta Gogliettino
Marco Balestrieri
Rosarita Tatè
Luigi Nicolais
Gianna Palmieri
author_sort Bruna Agrillo
collection DOAJ
description Antimicrobial peptides (AMPs) are excellent candidates to fight multi-resistant pathogens worldwide and are considered promising bio-preservatives to control microbial spoilage through food processing. To date, designing de novo AMPs with high therapeutic indexes, low-cost synthesis, high resistance, and bioavailability, remains a challenge. In this study, a novel decapeptide, named RiLK1, was rationally designed starting from the sequence of the previously characterized AMP 1018-K6, with the aim of developing short peptides, and promoting higher selectivity over mammalian cells, antibacterial activity, and structural resistance under different salt, pH, and temperature conditions. Interestingly, RiLK1 displayed a broad-spectrum of bactericidal activity against Gram-positive and Gram-negative bacteria, including multidrug resistant clinical isolates of <i>Salmonella</i> species, with Minimal Bactericidal Concentration (MBC) values in low micromolar range, and it was effective even against two fungal pathogens with no evidence of cytotoxicity on human keratinocytes and fibroblasts. Moreover, RiLK1-activated polypropylene films were revealed to efficiently prevent the growth of microbial spoilage, possibly improving the shelf life of fresh food products. These results suggested that de novo designed peptide RiLK1 could be the first candidate for the development of a promising class of decameric and multitask antimicrobial agents to overcome drug-resistance phenomena.
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spelling doaj.art-26012ba1fc464308bc6b179e74bcf9122023-11-20T14:36:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118695210.3390/ijms21186952A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional CharacterizationBruna Agrillo0Yolande T. R. Proroga1Marta Gogliettino2Marco Balestrieri3Rosarita Tatè4Luigi Nicolais5Gianna Palmieri6Materias Srl, 80146 Naples, ItalyDepartment of Food Microbiology, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, ItalyInstitute of Biosciences and BioResources, National Research Council (IBBR-CNR), 80131 Napoli, ItalyInstitute of Biosciences and BioResources, National Research Council (IBBR-CNR), 80131 Napoli, ItalyInstitute of Genetics and Biophysics, National Research Council (IGB-CNR), 80131 Naples, ItalyMaterias Srl, 80146 Naples, ItalyInstitute of Biosciences and BioResources, National Research Council (IBBR-CNR), 80131 Napoli, ItalyAntimicrobial peptides (AMPs) are excellent candidates to fight multi-resistant pathogens worldwide and are considered promising bio-preservatives to control microbial spoilage through food processing. To date, designing de novo AMPs with high therapeutic indexes, low-cost synthesis, high resistance, and bioavailability, remains a challenge. In this study, a novel decapeptide, named RiLK1, was rationally designed starting from the sequence of the previously characterized AMP 1018-K6, with the aim of developing short peptides, and promoting higher selectivity over mammalian cells, antibacterial activity, and structural resistance under different salt, pH, and temperature conditions. Interestingly, RiLK1 displayed a broad-spectrum of bactericidal activity against Gram-positive and Gram-negative bacteria, including multidrug resistant clinical isolates of <i>Salmonella</i> species, with Minimal Bactericidal Concentration (MBC) values in low micromolar range, and it was effective even against two fungal pathogens with no evidence of cytotoxicity on human keratinocytes and fibroblasts. Moreover, RiLK1-activated polypropylene films were revealed to efficiently prevent the growth of microbial spoilage, possibly improving the shelf life of fresh food products. These results suggested that de novo designed peptide RiLK1 could be the first candidate for the development of a promising class of decameric and multitask antimicrobial agents to overcome drug-resistance phenomena.https://www.mdpi.com/1422-0067/21/18/6952antimicrobial peptidefood pathogensfood packagingantifungal activityMDR <i>Salmonella</i> spp.
spellingShingle Bruna Agrillo
Yolande T. R. Proroga
Marta Gogliettino
Marco Balestrieri
Rosarita Tatè
Luigi Nicolais
Gianna Palmieri
A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional Characterization
International Journal of Molecular Sciences
antimicrobial peptide
food pathogens
food packaging
antifungal activity
MDR <i>Salmonella</i> spp.
title A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional Characterization
title_full A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional Characterization
title_fullStr A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional Characterization
title_full_unstemmed A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional Characterization
title_short A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional Characterization
title_sort safe and multitasking antimicrobial decapeptide the road from de novo design to structural and functional characterization
topic antimicrobial peptide
food pathogens
food packaging
antifungal activity
MDR <i>Salmonella</i> spp.
url https://www.mdpi.com/1422-0067/21/18/6952
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