2016
DOI: 10.1128/aac.01966-15
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An Amphipathic Undecapeptide with All d -Amino Acids Shows Promising Activity against Colistin-Resistant Strains of Acinetobacter baumannii and a Dual Mode of Action

Abstract: Multiple strains of Acinetobacter baumannii have developed multidrug resistance (MDR), leaving colistin as the only effective treatment. The cecropin-α-melittin hybrid BP100 (KKLFKKILKYL-NH2) and its analogs have previously shown activity against a wide array of plant and human pathogens. In this study, we investigated the in vitro antibacterial activities of 18 BP100 analogs (four known and 14 new) against the MDR A. baumannii strain ATCC BAA-1605, as well as against a number of other clinically relevant huma… Show more

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Cited by 34 publications
(35 citation statements)
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“…aureus-infected flies. These peptides are generally believed to work through electrostatic interactions with the negatively charged bacterial membrane (41, 42, 52, 53) and consequent pore formation, thereby disrupting the integrity of the bacterial membrane(s). This mechanism of action should exclude interaction with the more zwitterionic membranes of eukaryotic cells (52).…”
Section: Discussionmentioning
confidence: 99%
“…aureus-infected flies. These peptides are generally believed to work through electrostatic interactions with the negatively charged bacterial membrane (41, 42, 52, 53) and consequent pore formation, thereby disrupting the integrity of the bacterial membrane(s). This mechanism of action should exclude interaction with the more zwitterionic membranes of eukaryotic cells (52).…”
Section: Discussionmentioning
confidence: 99%
“…Addition of 200 M EDTA reduced the MIC of Art-175 and improved its antibacterial effect for all strains tested (ranging from Յ4 to 10 g/ml), providing a potentially interesting feature for topical applications. Colistin resistance (Ͼ2 to 4 g/ml) arises through addition of phosphoethanolamine or 4-amino-4-arabinose to the phosphate groups of the lipid A moiety of the lipopolysaccharides (19,20) and may thus directly affect the susceptibility to Art-175. However, no correlation was found between the MICs for colistin and Art-175 (n ϭ 28; R 2 ϭ 0.0043), indicating the lack of cross-resistance (see Table S2).…”
Section: Resultsmentioning
confidence: 99%
“…Lysis of human red blood cells (hRBCs) was measured as previously described . In brief, hRBCs from a freshly drawn type 0 negative blood sample were washed with PBS (pH 7.2, 10 mM Tris, 150 mM NaCl), followed by centrifugation at room temperature once at 700× g for 8 min, and then twice at 1000× g for 8 min each time.…”
Section: Methodsmentioning
confidence: 99%
“…Lysis of human red blood cells (hRBCs) was measured as previously described. 32 In brief, hRBCs from a freshly drawn type 0 negative blood sample were washed with PBS (pH 7.2, 10 mM Tris, 150 mM NaCl), followed by centrifugation at room temperature once at 700×g for 8 min, and then twice at 1000×g for 8 min each time. 17 Therefore, a selection of nine α-peptide/β-peptoid hybrids were initially designed and investigated to determine the effect of fluorination and length of side chains of the hydrophobic residues on the antibacterial activity against a panel of human and veterinary pathogens.…”
Section: Determination Of Hemolytic Activitymentioning
confidence: 99%