A broad-spectrum bactericidal lipopeptide with anti-biofilm properties

Scientific Reports
Ohad MeirAmram Mor

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, wer...Continue Reading

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Citations

May 19, 2018·Biomolecules·Athina AndreaHåvard Jenssen
Jul 6, 2019·Chemical Communications : Chem Comm·Apurva PanjlaSandeep Verma
Sep 15, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Joanna JammalAmram Mor
Apr 14, 2018·Frontiers in Plant Science·Sunil Kumar SahuNan Yao
Oct 3, 2020·International Journal of Molecular Sciences·Damian NeubauerWojciech Kamysz
Dec 24, 2020·International Journal of Molecular Sciences·Taylor Rounds, Suzana K Straus

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Datasets Mentioned

BETA
BAA-43
BAA-1720

Methods Mentioned

BETA
light scattering

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