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

Les aminoglycosides, tels que la streptomycine, sont de puissants antibiotiques bactéricides. Ces antibiotiques ciblent le ribosome bactérien, altérant la synthèse des protéines de multiples façons.La streptomicine se lie généralement à la sous-unité 30S du ribosome bactérien.Cette liaison provoque une distorsion conformationnelle, empêchant le bon alignement de l’ARNm et de l’ARNt initiateur.Cette distorsion empêche en outre la formation du complexe fonctionnel d’initiation 70S.En conséquence, les ribosomes restent arrêtés dans un état pré-initiation non fonctionnel.La streptomycine peut également affecter les ribosomes pendant la phase d’allongement. Cela peut faire que le ribosome interprète mal les codons ARNm et ajoute des acides aminés incorrects.Ces erreurs de traduction entraînent des protéines mal repliées ou tronquées qui peuvent s’insérer dans la membrane cellulaire bactérienne, modifiant sa perméabilité et conduisant à la mort cellulaire.De plus, la streptomycine peut bloquer les ribosomes lors de l’allongement dans une conformation inactive. Il arrête l’allongement et empêche le recyclage des ribosomes après la terminaison par translation.

inhibiteurs de la synthèse des protéines bactériennes

Inhibitors of Bacterial Protein Synthesis

Les aminochlorosides constituent une classe très puissante d’antibiotiques bactéricides qui exercent leurs effets antimicrobiens en ciblant le ribosome bactérien, perturbant spécifiquement la synthèse des protéines. Ces molécules polycationiques sont composées de sucres modifiés par des aminés, liés par des liaisons glycosidiques à un noyau d’aminocyclitol tel que la 2-désoxystreptamine ou la streptamine. Leurs fortes charges positives facilitent une liaison étroite à la colonne vertébrale phosphate chargée négativement de l’ARN ribosomique (ARNr), principalement au niveau de l’ARNr 16S de la sous-unité 30S du ribosome bactérien 70S.Mécanisme de la perturbation ribosomiale Des études structurales à haute résolution ont permis d’élucider que les aminochlorosides se lient au centre de décodage de la sous-unité 30S, en particulier autour de l’hélice 44 de l’ARNr 16S. Les nucléotides critiques impliqués dans cette interaction incluent A1408, A1492 et A1493. Lors de la liaison du médicament, ces résidus subissent des modifications conformationnelles qui stabilisent un état aberrant et retourné, même en présence d’ARNt quasi apparentés. Cette mauvaise régulation permet un couplage coden-anticodon incorrect, entraînant l’incorporation d’acides aminés erronés dans les peptides naissants et la génération de protéines mal repliées et dysfonctionnelles.Interférence avec la translation et la dynamique des ribosomes Au-delà de l’induction d’erreurs de traduction, certains aminochlorosides tels que la streptomycine interfèrent avec la formation d’un complexe fonctionnel d’initiation, entravent l’assemblage des sous-unités et entravent l’allongement en affectant la translocation médiée par EF-G. Le recyclage des ribosomes est également compromis car certains amino-sosides inhibent les actions concertées de RRF et EF-G nécessaires pour dissocier le complexe 70S. Cela aboutit à un blocage des ribosomes et à la séquestration des machines de translation.Conséquences cytotoxiques et résistance Les effets en aval incluent la désintégration de protéines membranaires aberrantes, entraînant une compromission de l’intégrité membranaire, une fuite d’ions et l’effondrement de la force motrice du proton et des niveaux d’ATP. Ces perturbations aboutissent à la mort cellulaire, distinguant les aminochlorosides des agents bactériostatiques. Les mécanismes de résistance ont évolué, notamment la modification enzymatique des médicaments, la méthylation des cibles, les mutations ribosomales et la réduction de l’absorption des médicaments. Des analyses structurelles détaillées continuent d’orienter le développement d’antibiotiques ciblant les ribosomes de nouvelle génération.

Inhibiteurs de la synthèse des protéines bactériennes

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

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Education

Enseignement

JoVE Core

Microbiology

Microbiologie

Unit

Unité

Antimicrobial Agents

Agents antimicrobiens

KEY TERMS AND CONCEPTS

TERMES ET CONCEPTS CLÉS

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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mechanism-of-antibiotic-resistance-in-mrsa

How Bacteria Outsmart Antibiotics

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Leishmaniasis and Trypanothione Reductase

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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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