バクテリアのリボソームを標的とする幅広いスペクトルのラッソペプチド抗生物質

Manoj Jangra^1,2,3, Dmitrii Y Travin^4,5, Elena V Aleksandrova⁶

¹David Braley Centre for Antibiotics Discovery, McMaster University, Hamilton, Ontario, Canada.

Nature

|March 27, 2025

まとめ

研究者達はラリオシジンという新種のラッソペプチド抗生物質を発見しましたこれらの化合物は細菌のリボソームを標的とし,タンパク質合成を阻害し,病原体に対する幅広い活性を示します.

科学分野:

微生物学
分子生物学
薬物の発見

背景:

ラッソペプチドは,リボソームで合成され,特異な結び目構造を持つ翻訳後のペプチドである.
様々な細菌のメカニズムを標的にすることが知られているが,ライボソーム阻害剤としてラッソペプチドは特定されていない.
リボソームは多くの抗菌剤の主要標的です

研究の目的:

抗菌性を持つ新しいラッソペプチドを特定し特徴づけること.
これらの新しい化合物の作用機構,特に細菌のタンパク質合成に対する効果を調査する.
細菌の病原体に対するこれらのラッソペプチドの治療的可能性を評価する

主な方法:

ラリオシジンとラリオシジンBの分離と特徴付け M2 について
バクテリアの増殖阻害検査と広範囲のスクリーニング
リボソームへの作用機構を決定するための構造的,遺伝的,生化学的分析.
マウス感染モデルにおける耐性メカニズム,自発的な耐性生成,およびin vivo有効性の評価

主要な成果:

ラリオシジンは,様々な病原体に対する広範囲の抗菌作用を示します.
ラリオシジンは小さなリボソームのサブユニットに結合し,16SリボソームRNAとアミノアシル- tRNAと相互作用する.
タンパク質合成の阻害は,転位と誤コード化の誘導を妨害することによって発生する.
ラリオシディンは一般的な抵抗機構に対する抵抗性,自発的な抵抗への低い傾向,ヒト細胞への毒性,および強力なin vivo活性を示しています.

結論:

ラリオシジンは,リボソームを標的とするラッソペプチド抗生物質の新種である.
これらの化合物は細菌のタンパク質合成を抑制する新しいメカニズムを提供します
ラリオシジンは耐性病原体と戦う新しい抗菌薬の開発に有望な化学的基盤を提供する.

さらに関連する動画

11:19

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses

Published on: February 25, 2011

19.8K

11:56

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids

Published on: May 4, 2018

12.4K

関連する概念動画

01:23

Types of RNA

62.9K

Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...

62.9K

02:24

Ribosome Profiling

3.4K

Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...

3.4K

01:56

Riboswitches

8.0K

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...

8.0K

01:23

Antimicrobial Proteins

841

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...

841

01:34

Directing Proteins to the Rough Endoplasmic Reticulum

7.0K

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...

7.0K

01:27

Ribosomes

7.1K

Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome...