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

Los aminoglucósidos, como la estreptomicina, son potentes antibióticos bactericidas. Estos antibióticos actúan contra el ribosoma bacteriano, dificultando la síntesis de proteínas de múltiples maneras.La estreptomicina suele unirse a la subunidad 30S del ribosoma bacteriano.Esta unión provoca una distorsión conformacional, impidiendo la correcta alineación del ARNm y el ARNt iniciador.La distorsión impide además la formación del complejo funcional de iniciación 70S.Como resultado, los ribosomas permanecen detenidos en un estado pre-inicio no funcional.La estreptomicina también puede afectar a los ribosomas durante la fase de alargamiento. Puede hacer que el ribosoma interprete mal los codones de ARNm y añada aminoácidos incorrectos.Estos errores traslacionales resultan en proteínas mal plegadas o truncadas que pueden insertarse en la membrana celular bacteriana, alterando su permeabilidad y conduciendo a la muerte celular.Además, la estreptomicina puede bloquear los ribosomas durante la elongación en una conformación inactiva. Detiene la elongación y evita el reciclaje de ribosomas tras la terminación por traslación.

inhibidores de la síntesis de proteínas bacterianas

Inhibitors of Bacterial Protein Synthesis

Los aminoglucósidos constituyen una clase altamente potente de antibióticos bactericidas que ejercen sus efectos antimicrobianos al atacar el ribosoma bacteriano, interrumpiendo específicamente la síntesis de proteínas. Estas moléculas policacionales consisten en azúcares aminomodificados enlazados mediante enlaces glicosídicos a un núcleo de aminociclitol, como la 2-desoxisrepttamina o la estreptamina. Sus fuertes cargas positivas facilitan una unión estrecha a la columna vertebral de fosfato cargada negativamente del ARN ribosómico (ARNr), principalmente en el ARNr 16S de la subunidad 30S del ribosoma bacteriano 70S.Mecanismo de la alteración ribosómica Estudios estructurales de alta resolución han aclarado que los aminoglucósidos se unen dentro del centro de decodificación de la subunidad 30S, especialmente alrededor de la hélice 44 del ARNr 16S. Los nucleótidos críticos implicados en esta interacción incluyen A1408, A1492 y A1493. Al unirse al fármaco, estos residuos sufren cambios conformacionales que estabilizan un estado aberrante y desorientado, incluso en presencia de ARNt casi cognados. Esta mala regulación permite un emparejamiento incorrecto codón-anticodón, lo que resulta en la incorporación de aminoácidos erróneos en péptidos incipientes y en la generación de proteínas mal plegadas y disfuncionales.Interferencia con la Dinámica de Traslación y Ribosomas Más allá de inducir errores traslacionales, ciertos aminoglucósidos, como la estreptomicina, interfieren en la formación de un complejo funcional de iniciación, dificultan la unión de subunidades y dificultan el alargamiento al afectar la translocación mediada por EF-G. El reciclaje de ribosomas también se ve comprometido, ya que algunos aminoglucósidos inhiben las acciones concertadas de RRF y EF-G necesarias para disociar el complejo 70S. Esto culmina en el estancamiento de ribosomas y la secuestración de la maquinaria traslacional.Consecuencias citotóxicas y resistencia Los efectos posteriores incluyen la desintegración de proteínas de membrana aberrantes, lo que conduce a una integridad membranera comprometida, fuga de iones y colapso de la fuerza motriz del protone y los niveles de ATP. Estas alteraciones culminan en la muerte celular, distinguiendo aminoglucósidos de agentes bacteriostáticos. Han evolucionado mecanismos de resistencia, incluyendo la modificación enzimática de fármacos, la metilación de objetivos, mutaciones ribosómicas y la reducción de la absorción de fármacos. Los conocimientos estructurales detallados continúan informando el desarrollo de antibióticos de próxima generación dirigidos a ribosomas.

Inhibidores de la síntesis 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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inhibitors-of-bacterial-protein-synthesis

Education

Educación

JoVE Core

Microbiology

Microbiología

Unit

Unidad

Antimicrobial Agents

Agentes antimicrobianos

KEY TERMS AND CONCEPTS

TÉRMINOS Y CONCEPTOS CLAVE

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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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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