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

Аминогликозиды, такие как стрептомицин, являются мощными бактерицидными антибиотиками. Эти антибиотики воздействуют на бактериальную рибосому, нарушая синтез белка различными способами.Стрептомицин обычно связывается с субъединицей 30S бактериальной рибосомы.Это связывание вызывает конформационное искажение, препятствуя правильному выравниванию мРНК и инициирующей тРНК.Искажение дополнительно препятствует формированию функционального комплекса инициации 70S.В результате рибосомы остаются в состоянии нефункционального прединициационного состояния.Стрептомицин также может влиять на рибосомы в фазе удлинения. Это может привести к тому, что рибосома будет неправильно читать мРНК-кодоны и добавлять неправильные аминокислоты.Эти трансляционные ошибки приводят к неправильному свернутому или усечённому белку, которые могут вставляться в мембрану бактериальной клетки, изменяя её проницаемость и приводя к гибели клеток.Кроме того, стрептомицин может блокировать рибосомы во время удлинения в неактивной конформации. Она останавливает удлинение и предотвращает повторение рибосом после завершения трансляции.

Ингибиторы синтеза бактериального белка

Inhibitors of Bacterial Protein Synthesis

Аминогликозиды представляют собой высокоэффективный класс бактерицидных антибиотиков, которые оказывают антимикробное действие, воздействуя на бактериальную рибосому, нарушая синтез белка. Эти поликатионные молекулы состоят из амино-модифицированных сахаров, связанных гликозидными связями с ядром аминоциклитола, таких как 2-дезоксистрептамин или стрептамин. Их сильные положительные заряды способствуют плотному связыванию с отрицательно заряженным фосфатным хребтом рибосомной РНК (рРНК), преимущественно в 16S рРНК субъединицы 30S в бактериальной рибосоме 70S.Механизм нарушения рибосомы Высококачественные структурные исследования показали, что аминогликозиды связываются в центре декодирования субъединицы 30S, особенно вокруг спирали 44 16S рРНК. Критические нуклеотиды, участвующие в этом взаимодействии, включают A1408, A1492 и A1493. При связывании препаратом эти остатки подвергаются конформационным изменениям, которые стабилизируют аномальное перевернутое состояние даже в присутствии близкородных тРНК. Эта неправильная регуляция приводит к неправильному сопряжению кодон-антикодон, что приводит к включению ошибочных аминокислот в зарождающиеся пептиды и образованию неправильно свернутых, дисфункциональных белков.Вмешательство в трансляцию и динамику рибосом Помимо индуцирования трансляционных ошибок, некоторые аминогликозиды, такие как стрептомицин, мешают формированию функционального инициационного комплекса, затрудняют соединение субъединиц и затрудняют удлинение, воздействуя на транслокацию, опосредованную EF-G. Рециркуляция рибосом также нарушена, поскольку некоторые аминогликозиды подавляют согласованное действие RRF и EF-G, необходимые для диссоциации комплекса 70S. Это приводит к задержке рибосом и секвестрации трансляционного механизма.Цитотоксические последствия и резистентность Последующие эффекты включают неправильную интеграцию аномальных мембранных белков, что приводит к нарушению целостности мембраны, утечке ионов и коллапсу движущей силы протона и уровней АТФ. Эти нарушения приводят к гибели клеток, отличая аминогликозиды от бактериостатических агентов. Механизмы устойчивости эволюционировали, включая модификацию ферментативного препарата, метилирование мишеней, мутации рибосом и снижение усвоения лекарств. Детальные структурные инсайты продолжают служить в основе разработки антибиотиков следующего поколения, направленных на рибосомы.

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

Микробиология

Unit

Единица

Antimicrobial Agents

Антимикробные препараты

KEY TERMS AND CONCEPTS

ОСНОВНЫЕ ТЕРМИНЫ И ПОНЯТИЯ

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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antifungal agents

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How Bacteria Outsmart Antibiotics

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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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