PGLa-H tandem-repeat peptides active against multidrug resistant clinical bacterial isolates
| Autor: | Juraj Simunić, Marija Tonkić, Marijana Mijaković, Alessandro Tossi, Tomislav Rončević, Goran Gajski, Ivana Goić-Barišić, Larisa Zoranić, Davor Juretić, Monica Benincasa, Nada Ilić |
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| Přispěvatelé: | Rončević, Tomislav, Gajski, Goran, Ilić, Nada, Goić Barišić, Ivana, Tonkić, Marija, Zoranić, Larisa, Simunić, Juraj, Benincasa, Monica, Mijaković, Marijana, Tossi, Alessandro, Juretić, Davor |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
DNA damage medicine.drug_class Cell Survival Antibiotics Antimicrobial peptides Biophysics Microbial Sensitivity Tests Cyto/genotoxicity Biology Molecular Dynamics Simulation Bactericidal activity Gram-Positive Bacteria Biochemistry Microbiology 03 medical and health sciences Tandem repeat Drug Resistance Multiple Bacterial Gram-Negative Bacteria medicine Humans Clinical isolates PGLa-H Multidrug resistant 030102 biochemistry & molecular biology Cell Biology Haemolysis In vitro Multiple drug resistance 030104 developmental biology Biophysic Antibacterial activity Peptides Antimicrobial peptide Clinical isolate Antimicrobial Cationic Peptides DNA Damage |
| Popis: | 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. Copyright A 2016 Elsevier B.V. All rights reserved. |
| Databáze: | OpenAIRE |
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