title: PGLa-H tandem-repeat peptides active against multidrug resistant clinical bacterial isolates.
abstract: Antimicrobial peptides (AMPs) are promising candidates for new antibiotic classes but often display an unacceptably high toxicity towards human cells. A naturally produced C-terminal fragment of PGLa, named PGLa-H, has been reported to have a very low haemolytic activity while maintaining a moderate antibacterial activity. A sequential tandem repeat of this fragment, diPGLa-H, was designed, as well as an analogue with a Val to Gly substitution at a key position. These peptides showed markedly improved in vitro bacteriostatic and bactericidal activity against both reference strains and multidrug resistant clinical isolates of Gram-negative and Gram-positive pathogens, with generally low toxicity for human cells as assessed by haemolysis, cell viability, and DNA damage assays. The glycine substitution analogue, kiadin, had a slightly better antibacterial activity and reduced haemolytic activity, which may correlate with an increased flexibility of its helical structure, as deduced using molecular dynamics simulations. These peptides may serve as useful lead compounds for developing anti-infective agents against resistant Gram-negative and Gram-positive species.
authors.affiliation: Department of Physics, Faculty of Science, University of Split, Split, Croatia.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Rončević
authors.affiliation: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
authors.forename: Goran
authors.initials: G
authors.lastname: Gajski
authors.affiliation: Department of Physics, Faculty of Science, University of Split, Split, Croatia.
authors.forename: Nada
authors.initials: N
authors.lastname: Ilić
authors.affiliation: Department of Clinical Microbiology, University Hospital Centre Split and University of Split School of Medicine, Split, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Goić-Barišić
authors.affiliation: Department of Clinical Microbiology, University Hospital Centre Split and University of Split School of Medicine, Split, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Tonkić
authors.affiliation: Department of Physics, Faculty of Science, University of Split, Split, Croatia.
authors.forename: Larisa
authors.initials: L
authors.lastname: Zoranić
authors.affiliation: Department of Physics, Faculty of Science, University of Split, Split, Croatia.
authors.forename: Juraj
authors.initials: J
authors.lastname: Simunić
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Benincasa
authors.affiliation: Department of Physics, Faculty of Science, University of Split, Split, Croatia.
authors.forename: Marijana
authors.initials: M
authors.lastname: Mijaković
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tossi
authors.affiliation: Department of Physics, Faculty of Science, University of Split, Split, Croatia; Mediterranean Institute for Life Sciences, Split, Croatia. Electronic address: davor.juretic@gmail.com.
authors.forename: Davor
authors.initials: D
authors.lastname: Juretić
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000494:pharmacology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D010455:Peptides
keywords: Antimicrobial peptides; Bactericidal activity; Clinical isolates; Cyto/genotoxicity; Multidrug resistant; PGLa-H