2023-03-06 シンガポール国立大学(NUS)
ナノネットは自己組織化ペプチドから作られ、抗生物質コリスチンにさえ耐性のあるバクテリアにも対応できる。
ナノネットは細菌特有の膜成分を特異的にターゲットとすることができ、トリプシンによる分解にも耐性がある。
ナノネットはこれまでにない特異性と堅牢性を持つため、抗生物質耐性を持つ細菌に対する新しい治療法として期待される。
研究者たちは、次の段階として、人間の臨床応用に向けた設計の最適化を目指している。
<関連情報>
- https://news.nus.edu.sg/trapping-and-killing-superbugs-with-nanonets/
- https://onlinelibrary.wiley.com/doi/10.1002/adfm.202210858
抗菌ペプチドナノネットの細菌応答性自己組織化による抗生物質耐性菌のトラップアンドキル化 Bacteria-Responsive Self-Assembly of Antimicrobial Peptide Nanonets for Trap-and-Kill of Antibiotic-Resistant Strains
Nhan Dai Thien Tram, Jian Xu, Devika Mukherjee, Antonio Eduardo Obanel, Venkatesh Mayandi, Vanitha Selvarajan, Xiao Zhu, Jeanette Teo, Veluchamy Amutha Barathi, Rajamani Lakshminarayanan, Pui Lai Rachel Ee
Advanced Functional Materials Published: 29 November 2022
DOI:https://doi.org/10.1002/adfm.202210858
Abstract
Bacterial trapping using nanonets is a ubiquitous immune defense mechanism against infectious microbes. These nanonets can entrap microbial cells, effectively arresting their dissemination and rendering them more vulnerable to locally secreted microbicides. Inspired by this evolutionarily conserved anti-infective strategy, a series of 15 to 16 residue-long synthetic β-hairpin peptides is herein constructed with the ability to self-assemble into nanonets in response to the presence of bacteria, enabling spatiotemporal control over microbial killing. Using amyloid-specific K114 assay and confocal microscopy, the membrane components lipoteichoic acid and lipopolysaccharide are shown to play a major role in determining the amyloid-nucleating capacity as triggered by Gram-positive and Gram-negative bacteria respectively. These nanonets displayed both trapping and killing functionalities, hence offering a direct improvement from the trap-only biomimetics in literature. By substituting a single turn residue of the non-amyloidogenic BTT1 peptide, the nanonet-forming BTT1-3A analog is produced with comparable antimicrobial potency. With the same sequence manipulation approach, BTT2-4A analog modified from BTT2 peptide showed improved antimicrobial potency against colistin-resistant clinical isolates. The peptide nanonets also demonstrated robust stability against proteolytic degradation, and promising in vivo efficacy and biosafety profile. Overall, these bacteria-responsive peptide nanonets are promising clinical anti-infective alternatives for circumventing antibiotic resistance.
