title: Biofilm eradication kinetics of the ultrashort lipopeptide C12 -OOWW-NH2 utilizing a modified MBEC Assay(™).
abstract: In this study, we report the antimicrobial planktonic and biofilm kill kinetics of ultrashort cationic lipopeptides previously demonstrated by our group to have a minimum biofilm eradication concentration (MBEC) in the microgram per mL (μg/mL) range against clinically relevant biofilm-forming micro-organisms. We compare the rate of kill for the most potent of these lipopeptides, dodecanoic (lauric) acid-conjugated C12 -Orn-Orn-Trp-Trp-NH2 against the tetrapeptide amide H-Orn-Orn-Trp-Trp-NH2 motif and the amphibian peptide Maximin-4 via a modification of the MBEC Assay(™) for Physiology & Genetics (P&G). Improved antimicrobial activity is achieved upon N-terminal lipidation of the tetrapeptide amide. Increased antimicrobial potency was demonstrated against both planktonic and biofilm forms of Gram-positive micro-organisms. We hypothesize rapid kill to be achieved by targeting of microbial membranes. Complete kill against established 24-h Gram-positive biofilms occurred within 4 h of exposure to C12 -OOWW-NH2 at MBEC values [methicillin-resistant Staphylococcus epidermidis (ATCC 35984): 15.63 μg/mL] close to the values for the planktonic minimum inhibitory concentration (MIC) [methicillin-resistant Staphylococcus epidermidis (ATCC 35984): 1.95 μg/mL]. Such rapid kill, especially against sessile biofilm forms, is indicative of a reduction in the likelihood of resistant strains developing with the potential for quicker resolution of pathogenic infection. Ultrashort antimicrobial lipopeptides have high potential as antimicrobial therapy.
authors.affiliation: Biomaterials, Biofilm and Infection Control Research Group, School of Pharmacy, Queens University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK.
authors.forename: Garry
authors.initials: G
authors.lastname: Laverty
authors.forename: Sean P
authors.initials: SP
authors.lastname: Gorman
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Gilmore
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000502:physiology; D055666:Lipopeptides / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D055666:Lipopeptides
keywords: antimicrobial; biofilm; kill kinetics; lipopeptides; minimum biofilm eradication concentration