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

Gli aminoglicosidi, come la streptomicina, sono potenti antibiotici battericidi. Questi antibiotici agiscono contro il ribosoma batterico, compromettendo la sintesi proteica in diversi modi.La streptomicina tipicamente si lega alla subunità 30S del ribosoma batterico.Questo legame provoca una distorsione conformazionale, impedendo il corretto allineamento dell'mRNA e del tRNA iniziatore.La distorsione impedisce ulteriormente la formazione del complesso funzionale di iniziazione 70S.Di conseguenza, i ribosomi rimangono bloccati in uno stato pre-iniziazione non funzionale.La streptomicina può anche influenzare i ribosomi durante la fase di allungamento. Può causare che il ribosoma interpreti male i codoni dell'mRNA e aggiunga amminoacidi scorretti.Questi errori di traduzione portano a proteine mal ripiegate o troncate che possono inserirsi nella membrana cellulare batterica, alterandone la permeabilità e portando alla morte cellulare.Inoltre, la streptomicina può bloccare i ribosomi durante l'allungamento in una conformazione inattiva. Ferma l'allungamento e impedisce il riciclo dei ribosomi dopo la terminazione della traslazione.

inibitori della sintesi proteica batterica

Inhibitors of Bacterial Protein Synthesis

Gli aminoglicosidi costituiscono una classe altamente potente di antibiotici battericidi che esercitano i loro effetti antimicrobici mirando al ribosoma batterico, interrompendo in particolare la sintesi proteica. Queste molecole policationiche sono costituite da zuccheri amminomodificati collegati tramite legami glicosidi a un nucleo di aminociclitolo come la 2-desossisreptamina o la streptamina. Le loro forti cariche positive facilitano un legame stretto alla spina dorsale fosfatica carica negativamente dell'RNA ribosomale (rRNA), principalmente al rRNA 16S della subunità 30S nel ribosoma batterico 70S.Meccanismo della Perturbazione Ribosomica Studi strutturali ad alta risoluzione hanno chiarito che gli aminoglicosidi si legano all'interno del centro di decodifica della subunità 30S, in particolare attorno all'elica 44 del rRNA 16S. I nucleotidi critici coinvolti in questa interazione includono A1408, A1492 e A1493. Al momento del legame del farmaco, questi residui subiscono cambiamenti conformazionali che stabilizzano uno stato aberrante e spento, anche in presenza di tRNA quasi cognatati. Questa cattiva regolazione permette un accoppiamento corretto: codone-anticodone, che porta all'incorporazione di amminoacidi errati nei peptidi nascenti e alla generazione di proteine mal ripiegate e disfunzionali.Interferenza con la Traduzione e la Dinamica dei Ribosomi Oltre a indurre errori di traduzione, alcuni aminoglicosidi come la streptomicina interferiscono con la formazione di un complesso di iniziazione funzionale, ostacolano l'unione delle subunità e ostacolano l'allungamento influenzando la traslocazione mediata da EF-G. Il riciclo dei ribosomi è inoltre compromesso poiché alcuni aminoglicosidi inibiscono le azioni concertate di RRF ed EF-G necessarie per dissociare il complesso 70S. Questo culmina in uno stallo del ribosoma e nel sequestro dei meccanismi traslazionali.Conseguenze e resistenza citotossica Gli effetti a valle includono la disintegrazione di proteine aberranti della membrana, che porta a compromesso dell'integrità della membrana, perdita di ioni e collasso della forza motrice protonica e dei livelli di ATP. Queste interruzioni culminano nella morte cellulare, distinguendo gli aminoglicosidi dagli agenti batteriostatici. Si sono evoluti meccanismi di resistenza, tra cui la modifica enzimatica dei farmaci, la metilazione del bersaglio, le mutazioni ribosomiche e la riduzione dell'assorbimento dei farmaci. Dettagliate informazioni strutturali continuano a guidare lo sviluppo di antibiotici di nuova generazione che mirano ai ribosomi.

Inibitori della sintesi proteica batterica

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

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Antimicrobial Agents

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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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inhibitors of bacterial protein synthesis

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...

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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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