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.

ADMET, absorption, distribution, metabolism and excretion – toxicity in pharmacokinetics; AMP, antimicrobial peptide; AMR, antimicrobial resistance; ATCC, ATCC cell collection; Antibiotic; 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; lipopeptide; mITT population, minimal intend-to-treat population; peptide antibiotic; s.c., subcutaneous.