Antimicrobial Activity of α-Peptide/β-Peptoid Lysine-Based Peptidomimetics Against Colistin-Resistant Isolated From Cystic Fibrosis Patients

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2019 Mar 8

PMID 30842761

Citations 10

Authors

Natalia Molchanova

Hengzhuang Wang

Paul R Hansen

Niels Hoiby

Hanne M Nielsen

Henrik Franzyk

Affiliations

Soon will be listed here.

Abstract

infection is a predominant cause of morbidity and mortality in patients with cystic fibrosis infection and with a compromised immune system. Emergence of bacterial resistance renders existing antibiotics inefficient, and therefore discovery of new antimicrobial agents is highly warranted. In recent years, numerous studies have demonstrated that antimicrobial peptides (AMPs) constitute potent agents against a range of pathogenic bacteria. However, AMPs possess a number of drawbacks such as susceptibility to proteolytic degradation with ensuing low bioavailability. To circumvent these undesired properties of AMPs unnatural amino acids or altered backbones have been incorporated to provide stable peptidomimetics with retained antibacterial activity. Here, we report on antimicrobial α-peptide/β-peptoid lysine-based peptidomimetics that exhibit high potency against clinical drug-resistant strains obtained from cystic fibrosis patients. These clinical strains possess and/or mutations that confer high resistance to colistin, the last-resort antibiotic for treatment of infections caused by . The lead peptidomimetic LBP-2 demonstrated a 12-fold improved anti-pseudomonal activity as compared to colistin sulfate as well as favorable killing kinetics, similar antibiofilm activity, and moderate cytotoxicity.

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