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

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  1. Involvement of NLRP3 and NLRC4 Inflammasome in Uropathogenic E. coli Mediated Urinary Tract Infections

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  2. Oxygen Restriction Generates Difficult-to-Culture P. aeruginosa

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  3. A Sporadic Four-Year Hospital Outbreak of a ST97-IVa MRSA With Half of the Patients First Identified in the Community

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  4. Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

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  5. Bacteria Display Differential Growth and Adhesion Characteristics on Human Hair Shafts

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  1. Azithromycin potentiates avian IgY effect against Pseudomonas aeruginosa in a murine pulmonary infection model

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  2. Early IL-2 treatment of mice with Pseudomonas aeruginosa pneumonia induced PMN-dominating response and reduced lung pathology

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  3. Biofilms of Mycobacterium abscessus complex can be sensitized to antibiotics by disaggregation and oxygenation

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  4. Primary ciliary dyskinesia patients have the same P. aeruginosa clone in sinuses and lungs

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Pseudomonas aeruginosa 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 P. aeruginosa strains obtained from cystic fibrosis patients. These clinical strains possess phoQ and/or pmrB mutations that confer high resistance to colistin, the last-resort antibiotic for treatment of infections caused by P. aeruginosa. 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.

Original languageEnglish
JournalFrontiers in Microbiology
Volume10
Pages (from-to)275
ISSN1664-302X
DOIs
Publication statusPublished - 2019

ID: 59045832