A broad-spectrum bactericidal lipopeptide with anti-biofilm properties

Abstract Previous studies of the oligoacyllysyl (OAK) series acyl-lysyl-lysyl-aminoacyl-lysine-amide, suggested their utility towards generating robust linear lipopeptide-like alternatives to antibiotics, although to date, none exhibited potent broad-spectrum bactericidal activity. To follow up on t...

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Autores principales:	Ohad Meir, Fadia Zaknoon, Uri Cogan, Amram Mor
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/85a31caf343a4e0caf632b0e4a2586e8
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spelling	oai:doaj.org-article:85a31caf343a4e0caf632b0e4a2586e82021-12-02T15:06:20ZA broad-spectrum bactericidal lipopeptide with anti-biofilm properties10.1038/s41598-017-02373-02045-2322https://doaj.org/article/85a31caf343a4e0caf632b0e4a2586e82017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02373-0https://doaj.org/toc/2045-2322Abstract Previous studies of the oligoacyllysyl (OAK) series acyl-lysyl-lysyl-aminoacyl-lysine-amide, suggested their utility towards generating robust linear lipopeptide-like alternatives to antibiotics, although to date, none exhibited potent broad-spectrum bactericidal activity. To follow up on this premise, we produced a new analog (C14KKc12K) and investigated its properties in various media. Mechanistic studies suggest that C14KKc12K uses a non-specific membrane-disruptive mode of action for rapidly reducing viability of Gram-negative bacteria (GNB) similarly to polymyxin B (PMB), a cyclic lipopeptide used as last resort antibiotic. Indeed, C14KKc12K displayed similar affinity for lipopolysaccharides and induced cell permeabilization associated with rapid massive membrane depolarization. Unlike PMB however, C14KKc12K was also bactericidal to Gram-positive bacteria (GPB) at or near the minimal inhibitory concentration (MIC), as assessed against a multispecies panel of >50 strains, displaying MIC50 at 3 and 6 µM, respectively for GPB and GNB. C14KKc12K retained activity in human saliva, reducing the viability of cultivable oral microflora by >99% within two minutes of exposure, albeit at higher concentrations, which, nonetheless, were similar to the commercial gold standard, chlorhexidine. This equipotent bactericidal activity was also observed in pre-formed biofilms of Streptococcus mutans, a major periodontal pathogen. Such compounds therefore, may be useful for eradication of challenging poly-microbial infections.Ohad MeirFadia ZaknoonUri CoganAmram MorNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ohad Meir Fadia Zaknoon Uri Cogan Amram Mor A broad-spectrum bactericidal lipopeptide with anti-biofilm properties
description	Abstract Previous studies of the oligoacyllysyl (OAK) series acyl-lysyl-lysyl-aminoacyl-lysine-amide, suggested their utility towards generating robust linear lipopeptide-like alternatives to antibiotics, although to date, none exhibited potent broad-spectrum bactericidal activity. To follow up on this premise, we produced a new analog (C14KKc12K) and investigated its properties in various media. Mechanistic studies suggest that C14KKc12K uses a non-specific membrane-disruptive mode of action for rapidly reducing viability of Gram-negative bacteria (GNB) similarly to polymyxin B (PMB), a cyclic lipopeptide used as last resort antibiotic. Indeed, C14KKc12K displayed similar affinity for lipopolysaccharides and induced cell permeabilization associated with rapid massive membrane depolarization. Unlike PMB however, C14KKc12K was also bactericidal to Gram-positive bacteria (GPB) at or near the minimal inhibitory concentration (MIC), as assessed against a multispecies panel of >50 strains, displaying MIC50 at 3 and 6 µM, respectively for GPB and GNB. C14KKc12K retained activity in human saliva, reducing the viability of cultivable oral microflora by >99% within two minutes of exposure, albeit at higher concentrations, which, nonetheless, were similar to the commercial gold standard, chlorhexidine. This equipotent bactericidal activity was also observed in pre-formed biofilms of Streptococcus mutans, a major periodontal pathogen. Such compounds therefore, may be useful for eradication of challenging poly-microbial infections.
format	article
author	Ohad Meir Fadia Zaknoon Uri Cogan Amram Mor
author_facet	Ohad Meir Fadia Zaknoon Uri Cogan Amram Mor
author_sort	Ohad Meir
title	A broad-spectrum bactericidal lipopeptide with anti-biofilm properties
title_short	A broad-spectrum bactericidal lipopeptide with anti-biofilm properties
title_full	A broad-spectrum bactericidal lipopeptide with anti-biofilm properties
title_fullStr	A broad-spectrum bactericidal lipopeptide with anti-biofilm properties
title_full_unstemmed	A broad-spectrum bactericidal lipopeptide with anti-biofilm properties
title_sort	broad-spectrum bactericidal lipopeptide with anti-biofilm properties
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/85a31caf343a4e0caf632b0e4a2586e8
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A broad-spectrum bactericidal lipopeptide with anti-biofilm properties

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