Description
Title: Short bovine lactoferrin-derived antimicrobial peptides designed to combat multidrug-resistant enterococcus faecium were tested.
Abstract: A significant drug-resistant nosocomial pathogen of widespread antibiotic abuse is Enterococcus faecium. Based on the primary antimicrobial motif of bovine lactoferrin, we created short, chemically straightforward antimicrobial peptides (AMPs) with a specific amino acid composition, fixed charge, and hydrophobicity ratio (LfcinB6). These peptides’ minimal inhibitory concentrations (MIC) ranged from 4 to 16 g/mL, and 5L and 6L (both 12 residues long) showed a narrow spectrum and strong antibacterial activity against drug-resistant E. faecium isolates. Peptides 5L and 6L disrupted pre-existing biofilms by 75% and 90%, respectively, at a concentration of 32 g/mL, respectively, in E. faecium strain C68. When exposed for 120 minutes at 40 g/mL, 5L reduced 1 107 E. faecium persister cells by 3 logs, while 6L completely eliminated them in 60. An essential biofilm gene called ace was significantly downregulated by 8 folds (p = 0.02) and 4 folds (p = 0.01) at 0.5 MIC in 5L and 6L, respectively. Peptides 5L and 6L both depolarized the E. faecium membrane at a concentration of 32 g/mL, boosted fluidity, and ultimately ruptured the membrane. At 8 g/mL, 5L physiologically changed the tricarboxylic acid cycle, glutathione synthesis, and purine metabolism. Intriguingly, 5L (at 10 MIC) completely eliminated all 1 106 exponential and persister E. faecium cells in an ex vivo model of porcine skin infection, compared to no treatment (p = 0.0045 and p = 0.0002, respectively). In summary, the study presents peptide 5L as a potential therapeutic candidate to be investigated against E. faecium and provides a roadmap for the development of narrow-spectrum selective AMPs.
Keywords: antimicrobial peptides; biofilm; persisters; Enterococcus faecium
Paper Quality: SCOPUS / Web of Science Level Research Paper
Subject: Antibiotics
Writer Experience: 20+ Years
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