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

Aminoglicosídeos, como a estreptomicina, são antibióticos bactericidas potentes. Esses antibióticos atuam no ribossomo bacteriano, prejudicando a síntese proteica de várias formas.A estreptomicina normalmente se liga à subunidade 30S do ribossomo bacteriano.Essa ligação causa uma distorção conformacional, impedindo o alinhamento correto do mRNA com o tRNA iniciador.A distorção ainda impede a formação do complexo funcional de iniciação 70S.Como resultado, os ribossomos permanecem parados em um estado pré-início não funcional.A estreptomicina também pode afetar os ribossomos durante a fase de alongamento. Isso pode fazer com que o ribossomo leia mal os códons de mRNA e adicione aminoácidos incorretos.Esses erros de tradução resultam em proteínas mal dobradas ou truncadas que podem se inserir na membrana celular bacteriana, alterando sua permeabilidade e levando à morte celular.Além disso, a estreptomicina pode travar os ribossomos durante a elongação em uma conformação inativa. Ela interrompe o alongamento e impede a reciclagem dos ribossomos após a terminação da translação.

inibidores da síntese de proteínas bacterianas

Inhibitors of Bacterial Protein Synthesis

Os aminoglicosídeos constituem uma classe altamente potente de antibióticos bactericidas que exercem seus efeitos antimicrobianos ao atacar o ribossomo bacteriano, interrompendo especificamente a síntese de proteínas. Essas moléculas policationicas consistem em açúcares aminomodificados ligados por ligações glicosídicas a um núcleo de aminociclitol, como 2-desoxisrepttamina ou estreptamina. Suas fortes cargas positivas facilitam uma ligação apertada à espinha dorsal fosfatada carregada negativamente do RNA ribasomal (rRNA), principalmente no rRNA 16S da subunidade 30S do ribossomo bacteriano 70S.Mecanismo da Ruptura Ribossomal Estudos estruturais de alta resolução elucidaram que os aminoglicosídeos se ligam dentro do centro de decodificação da subunidade 30S, particularmente ao redor da hélice 44 do rRNA 16S. Nucleotídeos críticos envolvidos nessa interação incluem A1408, A1492 e A1493. Após a ligação do medicamento, esses resíduos passam por mudanças conformacionais que estabilizam um estado aberrante e invertido, mesmo na presença de tRNAs quase cognatos. Essa má regulação permite o pareamento incorreto de codon-anticodon, resultando na incorporação de aminoácidos errôneos em peptídeos nascentes e na geração de proteínas mal dobradas e disfuncionais.Interferência com a Tradução e a Dinâmica dos Ribossomos Além de induzir erros de tradução, certos aminoglicosídeos, como a estreptomicina, interferem na formação de um complexo funcional de iniciação, dificultam a união das subunidades e dificultam o alongamento ao afetar a translocação mediada pelo EF-G. A reciclagem de ribossomos também é comprometida, pois alguns aminoglicossimos inibem as ações concertadas do RRF e EF-G necessárias para dissociar o complexo 70S. Isso culmina em estagnação dos ribossomos e sequestro de máquinas translacionalistas.Consequências e Resistência Citotóxica Os efeitos a jusante incluem a desintegração de proteínas membranares aberrantes, levando a comprometida integridade da membrana, vazamento de íons e colapso da força motriz do próton e dos níveis de ATP. Essas perturbações culminam na morte celular, distinguindo aminoglicosídeos de agentes bacteriostáticos. Mecanismos de resistência evoluíram, incluindo modificação enzimática de medicamentos, metilação de alvos, mutações ribossomicas e redução na absorção de medicamentos. Insights estruturais detalhados continuam a informar o desenvolvimento de antibióticos de próxima geração que visam ribossomos.

Inibidores da Síntese de Proteínas Bacterianas

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

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JoVE Core

Microbiology

Microbiologia

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Antimicrobial Agents

Agentes Antimicrobianos

KEY TERMS AND CONCEPTS

TERMOS E CONCEITOS-CHAVE

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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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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