Name: aminoglycosides: how they stop bacteria
Uploaded: 2026-03-12T13:36:04.000Z
Duration: 1 min 25 s
Channel: JoVE

ストレプトマイシンのようなアミノグリコシドは強力な殺菌性抗生物質です。これらの抗生物質は細菌リボソームを標的にし、タンパク質合成を多方面で妨げます。ストレプトマイシンは通常、細菌リボソームの30Sサブユニットに結合します。この結合によって立体構造の歪みが生じ、mRNAとイニシエーターtRNAの適切な配列が妨げられます。この歪みは機能的な70S起始複合体の形成をさらに妨げます。その結果、リボソームは機能しない前開始状態のまま停止したままです。ストレプトマイシンは伸長期のリボソームにも影響を及ぼします。リボソームがmRNAコドンを誤読し、誤ったアミノ酸を加えることがあります。これらの翻訳エラーにより、誤った折りたたみや切断されたタンパク質が細菌の細胞膜に挿入され、透過性が変化し、細胞死を引き起こします。さらに、ストレプトマイシンは不活性な立体構造の伸長時にリボソームをロックすることがあります。これは伸長を止め、翻訳終了後のリボソームのリサイクルを防ぎます。

細菌タンパク質合成阻害剤

Inhibitors of Bacterial Protein Synthesis

アミノグリコシドは、細菌リボソームを標的にしてタンパク質合成を妨げることで抗菌効果を発揮する、非常に強力な殺菌性抗生物質のクラスです。これらのポリカチオン分子は、アミノ修飾糖がグリコシド結合を介して2-デオキシストレプタミンやストレプタミンなどのアミノサイクリトールコアに結合しています。これらの強い正電荷は、主に細菌の70Sリボソームの30Sサブユニットの16S rRNAに、負に帯電したリン酸骨格(rRNA)との緊密結合を促進します。リボソーム破壊のメカニズム 高解像度の構造研究により、アミノグリコシドが30Sサブユニットのデコード中心、特に16S rRNAのヘリックス44付近に結合することが明らかになりました。この相互作用に関与する重要なヌクレオチドにはA1408、A1492、A1493があります。薬物結合後、これらの残基は構体構造変化を起こし、ほぼ同根のtRNAが存在する場合でも異常な反逆状態を安定化させます。この誤調により、誤ったコドン-アンチコドンのペアリングが起こり、誤ったアミノ酸が新生ペプチドに組み込まれ、誤った折りたたみで機能不全なタンパク質が生成されます。翻訳およびリボソーム動態への干渉 翻訳エラーを引き起こすだけでなく、ストレプトマイシンのような特定のアミノグリコシドは機能的起始複合体の形成を妨げ、サブユニットの結合を妨げ、EF-G媒介の転座に影響を与えることで伸長を妨げます。リボソームのリサイクルも妨げられます。なぜなら、一部のアミノグリコシドが70S複合体を解離するために必要なRRFとEF-Gの協調作用を阻害するためです。最終的にリボソームの停滞と翻訳機構の隔離に至ります。細胞毒性の影響と耐性 その下流の影響として、異常な膜タンパク質の誤統合が起こり、膜の完全性が損なわれ、イオン漏れが起こり、陽子推進力やATPレベルの崩壊が生じます。これらの撹乱は細胞死に至り、アミノグリコシドと細菌抑制剤を区別します。耐性機構は進化しており、酵素的薬物修飾、標的メチル化、リボソーム変異、薬物取り込みの減少などが含まれます。詳細な構造的知見は次世代リボソーム標的抗生物質の開発に引き続き役立っています。

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, ...

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inhibitors-of-bacterial-protein-synthesis

Education

JoVE Core

Microbiology

微生物学

Unit

ユニット

Antimicrobial Agents

抗微生物剤

KEY TERMS AND CONCEPTS

主要な用語と概念

aminoglycosides: how they stop bacteria

Aminoglycosides are bactericidal antibiotics that stop bacteria by targeting the ribosome and disrupting protein synthesis. They are highly potent drugs made of amino-modified sugars linked by glycosidic bonds to an aminocyclitol core, such as 2-deoxystreptamine or streptamine. Their strong positive charge helps them bind tightly to the negatively charged phosphate backbone of ribosomal RNA, especially the 16S rRNA of the 30S subunit in the bacterial 70S ribosome.

These antibiotics act at the decoding center of the 30S subunit, near helix 44 of 16S rRNA. Key nucleotides in this region include A1408, A1492, and A1493. When aminoglycosides bind, these residues shift into an abnormal flipped-out state, even when near-cognate tRNAs are present. That change allows incorrect codon-anticodon pairing and leads to the addition of wrong amino acids to growing peptides.

The result is the production of misfolded, dysfunctional proteins. Some aminoglycosides, such as streptomycin, also interfere with other steps in translation. They can block formation of a functional initiation complex, prevent subunit joining, and slow elongation by affecting EF-G-mediated translocation. Ribosome recycling is also reduced because some aminoglycosides block the actions of RRF and EF-G that separate the 70S complex.

These problems cause ribosome stalling and trap the translation machinery. Faulty membrane proteins can then be inserted into the cell membrane, which weakens membrane integrity and causes ion leakage. This disruption collapses the proton motive force and lowers ATP levels. In the end, the bacterial cell dies, which is why aminoglycosides are bactericidal rather than bacteriostatic.

Bacteria can resist these drugs in several ways. They may chemically modify the antibiotic, methylate the target, change ribosomal sites through mutations, or reduce drug uptake. Structural studies of aminoglycoside binding continue to guide the design of next-generation antibiotics that target the ribosome.

Aminoglycosides: How They Stop Bacteria

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key terms and concepts

Learn how aminoglycosides bind bacterial rRNA, cause translation errors, disrupt ribosome recycling, and kill bacteria in this high school science page.

Aminoglycosides: How They Stop Bacteria | JoVE K12

JoVE Core Microbiology provides an engaging introduction to the microbial world and its influence on health, industry, and the environment. This comprehensive collection covers key concepts such as microbial structure, metabolism, genetics, and ecology. It introduces essential laboratory techniques and microscopy methods through visually engaging animations. Corresponding scientist-in-action videos bridge classroom concepts with real-world research and applications.

microbiology

Aminoglycosides: How They Stop Bacteria

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