Bovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates

Abstract Multidrug-resistant (MDR) Salmonella is a threat to public health. Non-antibiotic therapies could serve as important countermeasures to control MDR Salmonella outbreaks. In this study, antimicrobial activity of cationic α-helical bovine NK-lysin-derived antimicrobial peptides was evaluated...

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Autores principales:	Rohana P. Dassanayake, Briony M. Atkinson, Adam S. Mullis, Shollie M. Falkenberg, Eric M. Nicholson, Eduardo Casas, Balaji Narasimhan, Shawn M. D. Bearson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06b426dbf1ce4e95960f64be658c10ea
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spelling	oai:doaj.org-article:06b426dbf1ce4e95960f64be658c10ea2021-12-02T18:51:35ZBovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates10.1038/s41598-021-98860-62045-2322https://doaj.org/article/06b426dbf1ce4e95960f64be658c10ea2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98860-6https://doaj.org/toc/2045-2322Abstract Multidrug-resistant (MDR) Salmonella is a threat to public health. Non-antibiotic therapies could serve as important countermeasures to control MDR Salmonella outbreaks. In this study, antimicrobial activity of cationic α-helical bovine NK-lysin-derived antimicrobial peptides was evaluated against MDR Salmonella outbreak isolates. NK2A and NK2B strongly inhibited MDR Salmonella growth while NK1 and NK2C showed minimum-to-no growth inhibition. Scrambled-NK2A, which is devoid of α-helicity but has the same net positive charge as NK2A, also failed to inhibit bacterial growth. Incubation of negatively charged MDR Salmonella with NK2A showed increased Zeta potential, indicating bacterial-peptide electrostatic attraction. Confocal and transmission electron microscopy studies revealed NK2A-mediated damage to MDR Salmonella membranes. LPS inhibited NK2A-mediated growth suppression in a dose-dependent response, suggesting irreversible NK2A-LPS binding. LPS-NK2A binding and bacterial membrane disruption was also confirmed via electron microscopy using gold nanoparticle-NK2A conjugates. Finally, NK2A-loaded polyanhydride nanoparticles showed sustained peptide delivery and anti-bacterial activity. Together, these findings indicate that NK2A α-helicity and positive charge are prerequisites for antimicrobial activity and that MDR Salmonella killing is mediated by direct interaction of NK2A with LPS and the inner membrane, leading to bacterial membrane permeabilization. With further optimization using nano-carriers, NK2A has the potential to become a potent anti-MDR Salmonella agent.Rohana P. DassanayakeBriony M. AtkinsonAdam S. MullisShollie M. FalkenbergEric M. NicholsonEduardo CasasBalaji NarasimhanShawn M. D. BearsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rohana P. Dassanayake Briony M. Atkinson Adam S. Mullis Shollie M. Falkenberg Eric M. Nicholson Eduardo Casas Balaji Narasimhan Shawn M. D. Bearson Bovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates
description	Abstract Multidrug-resistant (MDR) Salmonella is a threat to public health. Non-antibiotic therapies could serve as important countermeasures to control MDR Salmonella outbreaks. In this study, antimicrobial activity of cationic α-helical bovine NK-lysin-derived antimicrobial peptides was evaluated against MDR Salmonella outbreak isolates. NK2A and NK2B strongly inhibited MDR Salmonella growth while NK1 and NK2C showed minimum-to-no growth inhibition. Scrambled-NK2A, which is devoid of α-helicity but has the same net positive charge as NK2A, also failed to inhibit bacterial growth. Incubation of negatively charged MDR Salmonella with NK2A showed increased Zeta potential, indicating bacterial-peptide electrostatic attraction. Confocal and transmission electron microscopy studies revealed NK2A-mediated damage to MDR Salmonella membranes. LPS inhibited NK2A-mediated growth suppression in a dose-dependent response, suggesting irreversible NK2A-LPS binding. LPS-NK2A binding and bacterial membrane disruption was also confirmed via electron microscopy using gold nanoparticle-NK2A conjugates. Finally, NK2A-loaded polyanhydride nanoparticles showed sustained peptide delivery and anti-bacterial activity. Together, these findings indicate that NK2A α-helicity and positive charge are prerequisites for antimicrobial activity and that MDR Salmonella killing is mediated by direct interaction of NK2A with LPS and the inner membrane, leading to bacterial membrane permeabilization. With further optimization using nano-carriers, NK2A has the potential to become a potent anti-MDR Salmonella agent.
format	article
author	Rohana P. Dassanayake Briony M. Atkinson Adam S. Mullis Shollie M. Falkenberg Eric M. Nicholson Eduardo Casas Balaji Narasimhan Shawn M. D. Bearson
author_facet	Rohana P. Dassanayake Briony M. Atkinson Adam S. Mullis Shollie M. Falkenberg Eric M. Nicholson Eduardo Casas Balaji Narasimhan Shawn M. D. Bearson
author_sort	Rohana P. Dassanayake
title	Bovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates
title_short	Bovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates
title_full	Bovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates
title_fullStr	Bovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates
title_full_unstemmed	Bovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates
title_sort	bovine nk-lysin peptides exert potent antimicrobial activity against multidrug-resistant salmonella outbreak isolates
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/06b426dbf1ce4e95960f64be658c10ea
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Bovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates

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