抗生物質耐性を弱める薬剤を研究者らが開発 Researchers have developed a drug that undercuts antibiotic resistance
2023-04-17 フィンランド・アールト大学
この新しい治療法は、抗生物質耐性の問題に取り組むための新しいツールとして期待される。研究チームは、細菌の外膜を弱体化させることで、抗生物質の効果を高める効果も示唆している。
これにより、既存の抗生物質を有効に維持することができ、抗生物質耐性の悪化を防ぐことができる可能性がある。しかし、臨床試験前には、さらなる研究が必要である。
<関連情報>
- https://www.aalto.fi/en/news/a-new-treatment-for-multidrug-resistant-bacteria
- https://www.nature.com/articles/s41467-023-37749-6
多剤耐性緑膿菌およびAcinetobacter baumanniiの病原性を封じ込め、バイオフィルムを根絶するためのホスト-ゲスト化学の再利用 Repurposing host-guest chemistry to sequester virulence and eradicate biofilms in multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii
Christopher Jonkergouw,Ngong Kodiah Beyeh,Ekaterina Osmekhina,Katarzyna Leskinen,S. Maryamdokht Taimoory,Dmitrii Fedorov,Eduardo Anaya-Plaza,Mauri A. Kostiainen,John F. Trant,Robin H. A. Ras,Päivi Saavalainen & Markus B. Linder
Nature Communications Published:14 April 2023
DOI:https://doi.org/10.1038/s41467-023-37749-6
Abstract
The limited diversity in targets of available antibiotic therapies has put tremendous pressure on the treatment of bacterial pathogens, where numerous resistance mechanisms that counteract their function are becoming increasingly prevalent. Here, we utilize an unconventional anti-virulence screen of host-guest interacting macrocycles, and identify a water-soluble synthetic macrocycle, Pillar[5]arene, that is non-bactericidal/bacteriostatic and has a mechanism of action that involves binding to both homoserine lactones and lipopolysaccharides, key virulence factors in Gram-negative pathogens. Pillar[5]arene is active against Top Priority carbapenem- and third/fourth-generation cephalosporin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, suppressing toxins and biofilms and increasing the penetration and efficacy of standard-of-care antibiotics in combined administrations. The binding of homoserine lactones and lipopolysaccharides also sequesters their direct effects as toxins on eukaryotic membranes, neutralizing key tools that promote bacterial colonization and impede immune defenses, both in vitro and in vivo. Pillar[5]arene evades both existing antibiotic resistance mechanisms, as well as the build-up of rapid tolerance/resistance. The versatility of macrocyclic host-guest chemistry provides ample strategies for tailored targeting of virulence in a wide range of Gram-negative infectious diseases.
