Health & Environmental Research Online (HERO)


Print Feedback Export to File
7188185 
Journal Article 
Antimicrobial Activity of alpha-Peptide/beta-Peptoid Lysine-Based Peptidomimetics Against Colistin-Resistant Pseudomonas aeruginosa Isolated From Cystic Fibrosis Patients 
Molchanova, N; Wang, H; Hansen, PR; Hoiby, N; Nielsen, HM; Franzy, H; , 
2019 
Yes 
Frontiers in Microbiology
ISSN: 1664-302X 
FRONTIERS MEDIA SA 
LAUSANNE 
10 
275 
English 
30842761 
WOS:000459114600001 
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 alpha-peptide/beta-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.