Emerging peptide antibiotics with therapeutic potential.
This review covers some of the recent progress in the field of peptide antibiotics with a focus on compounds with novel or established mode of action and with demonstrated efficacy in animal infection models. Novel drug discovery approaches, linear and macrocyclic peptide antibiotics, lipopeptides like the polymyxins as well as peptides addressing targets located in the plasma membrane or in the outer membrane of bacterial cells are discussed.
['Upert|Gregory|G|', 'Luther|Anatol|A|', 'Obrecht|Daniel|D|', 'Ermert|Philipp|P|']
peptide antibiotic Antibiotic lipopeptide ADMET, absorption, distribution, metabolism and excretion – toxicity in pharmacokinetics AMP, antimicrobial peptide AMR, antimicrobial resistance ATCC, ATCC cell collection BAM, β-barrel assembly machinery CC50, cytotoxic concentration to kill 50% of cells CD, circular dichroism CFU, colony forming unit CLSI, clinical and laboratory standards institute CMS, colistin methane sulfonate DMPC, 1,2-dimyristoyl-sn-glycero-3-phosphocholine ESKAPE, acronym encompassing six bacterial pathogens (often carrying antibiotic resistance): Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp FDA, U. S. Food and Drug Administration HABP, hospital acquired bacterial pneumonia HDP, host-defense peptide HEK293, human embryonic kidney 293 cells HK-2, human kidney 2 cells (proximal tubular cell line) HepG2, human hepatocellular carcinoma cell line Hpg, 4-hydroxy-phenyl glycine ITC, isothermal titration calorimetry KPC, Klebsiella pneumoniae metallo-β-lactamase C resistant LPS, lipopolysaccharide LptA, lipopolysaccharide transport protein A LptC, lipopolysaccharide transport protein C LptD, lipopolysaccharide transport protein D MDR, multidrug-resistant MH-I, Müller-Hinton broth I MH-II, Müller-Hinton broth II (cation adjusted) MIC, minimal inhibitory concentration MRSA, methicilline-resistant S. aureus MSSA, methicilline-sensitive S. aureus MoA, mechanism (mode) of action NDM-1, New Delhi metallo-β-lactamase resistant NOAEL, no adverse effect level ODL, odilorhabdin OMPTA (outer membrane targeting antibiotic) OMPTA, outer membrane targeting antibiotic Omp, outer membrane protein PBMC, peripheral mononuclear blood cell PBP, penicillin-binding protein PBS, phosphate-buffered saline PK, pharmacokinetics POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine POPG, 2-oleoyl-1-palmitoyl-sn-glycero-3-phospho-(1-glycerol) PrAMPs, polyproline antimicrobial peptides RBC, red blood cell SAR, structure-activity relationship SPR, surface plasmon resonance SPase I, signal peptidase I VABP, ventilator associated bacterial pneumonia VIM-1, beta-lactamase 2 (K. pneumoniae) VISA, vancomycin-intermediate S. aureus VRE, vancomycin-resistant enterococcus WHO, World Health Organization WT, wild type WTA, wall teichoic acid XDR, extremely drug-resistant antimicrobial peptide antimicrobial resistance bid, bis in die (two times a day) i.p., intraperitoneal i.v., intravenous mITT population, minimal intend-to-treat population s.c., subcutaneous