A biomimetic peptide recognizes and traps bacteria in vivo as human defensin-6

Abstract

Using broad-spectrum antibiotics for microbial infection may cause flora disequilibrium, drug-resistance, etc., seriously threatening human health. Here, we design a human defensin-6 mimic peptide (HDMP) that inhibits bacterial invasion in vivo through mimicking the mechanisms of human defensin-6 with high efficiency and precision. The HDMP with ligand and self-assembling peptide sequence recognizes bacteria through ligand-receptor interactions and subsequently traps bacteria by an in situ adaptive self-assembly process and resulting nanofibrous networks; these trapped bacteria are unable to invade host cells. In four animal infection models, the infection rate was markedly decreased. Notably, administration of HDMP (5 mg/kg) nanoparticles increased the survival rate of mice with methicillin-resistant S. aureus bacteremia by as much as 100%, even more than that of vancomycin treatment (5 mg/kg, 83.3%)–treated group, the golden standard of antibiotics. This biomimetic peptide shows great potential as a precise and highly efficient antimicrobial agent.

Antimicrobial peptides-An alternative candidates to antibiotics against Staphylococcus aureus and its antibiotic-resistant strains

“…This mechanism was apparent with both S. aureus-and MRSA-infected BALB/c mouse model. However, HDMP is active only against gram-positive bacteria but not against gram-negative bacteria [163]. Thus, these in vivo studies helped to understand the activity of this peptide in the live system.…”

Size‐Transformable Nanostructures: From Design to Biomedical Applications

“…Recently, Fan et al constructed a human defensin-6 mimic peptide (HDMP) containing 1) the RLYLRIGRR peptide sequence to bind to lipoteichoic acid (LTA) of Gram-positive bacteria, 2) KLVFF for the formation of fibrous structures, and 3) BP for imaging and increasing the hydrophobicity of the structure (Figure 8a). [63] HDMP first self-assembled into nanospheres, and it could then transform into nanofibers when it specifically bound to the LTA of Staphylococcus aureus (Figure 8b). Compared to the control system C-HDMP that could not form nanofibers upon interaction with LTA, HDMP nanoparticles could effectively trap the bacteria due to the formation of fibrous networks (Figure 8c,d), thus inhibiting bacterial invasion (Figure 8e,f).…”

“…Reproduced with permission. [63] Copyright 2020, The Authors, published by American Association for the Advancement of Science (AAAS). Reprinted/adapted from ref.…”

“…Reprinted/adapted from ref. [63]. © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.…”

De Novo Design of a pH-triggered Self-assembled β-hairpin Nano Peptide for the Dual Biological Function of Antibacterial and Entrapment

“…Among them, β-sheet peptides are more likely to self-assemble into brous structures due to the large presence of hydrogen bonds [5], as is seen in amyloid diseases such as Alzheimer's disease and Parkinson's disease [20]. These β-brous proteins have been determined to show potent antimicrobial activity and propensity for entrapping and agglutinating bacteria [21], preventing bacterial invasion into histocytes and promoting pathogen phagocytosis [22], which play important roles in human innate immunity to maintain microbiota homeostasis of the intestine [23,24]. However, few studies have reported the pH-triggered microstructural transformation and biological properties of β-hairpin self-assembled peptides.…”