Antibacterial efficacy of an ultra-short palmitoylated random peptide mixture in mouse models of infection by carbapenem-resistant Klebsiella pneumoniae .
Jonathan Z LauShanny Hsuan KuoYael BeloEinav MalachBar MaronHannah E CarawayMyung Whan OhYi ZhangNahed IsmailGee W LauZvi HayoukaPublished in: Antimicrobial agents and chemotherapy (2023)
Indiscriminate use of antibiotics has imposed a selective pressure for the rapid rise in bacterial resistance, creating an urgent need for novel therapeutics for managing bacterial infectious diseases while counteracting bacterial resistance. Carbapenem-resistant Klebsiella pneumoniae strains have become a major challenge in modern medicine due to their ability to cause an array of severe infections. Recently, we have shown that the 20-mer random peptide mixtures are effective therapeutics against three ESKAPEE pathogens. Here, we evaluated the toxicity, biodistribution, bioavailability, and efficacy of the ultra-short palmitoylated 5-mer phenylalanine:lysine (FK5P) random peptide mixtures against multiple clinical isolates of carbapenem-resistant K. pneumoniae and K. oxytoca . We demonstrate the FK5P rapidly and effectively killed various strains of K. pneumoniae , inhibited the formation of biofilms, and disrupted mature biofilms. FK5P displayed strong toxicity profiles both in vitro and in mice, with prolonged favorable biodistribution and a long half-life. Significantly, FK5P reduced the bacterial burden in mouse models of acute pneumonia and bacteremia and increased the survival rate in a mouse model of bacteremia. Our results demonstrate that FK5P is a safe and promising therapy against Klebsiella species as well as other ESKAPEE pathogens.
Keyphrases
- klebsiella pneumoniae
- mouse model
- escherichia coli
- multidrug resistant
- gram negative
- infectious diseases
- high resolution
- oxidative stress
- small molecule
- candida albicans
- pet imaging
- liver failure
- intensive care unit
- respiratory failure
- high throughput
- drug induced
- respiratory tract
- metabolic syndrome
- risk factors
- type diabetes
- skeletal muscle
- silver nanoparticles
- bone marrow
- single cell
- insulin resistance
- mesenchymal stem cells
- smoking cessation
- positron emission tomography
- high fat diet induced