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

Aminoglycosides, such as streptomycin, are potent bactericidal antibiotics. These antibiotics target the bacterial ribosome, impairing protein synthesis in multiple ways.Streptomycin typically binds to the 30S subunit of the bacterial ribosome.This binding causes a conformational distortion, preventing the proper alignment of mRNA and the initiator tRNA.The distortion further prevents the formation of the functional 70S initiation complex.As a result, the ribosomes remain arrested in a non-functional pre-initiation state.Streptomycin can also affect ribosomes during the elongation phase. It can cause the ribosome to misread mRNA codons and add incorrect amino acids.These translational errors result in misfolded or truncated proteins that can insert into the bacterial cell membrane, altering its permeability and leading to cell death.Additionally, streptomycin can lock the ribosomes during elongation in an inactive conformation. It halts elongation and prevents ribosome recycling after translation termination.

inhibitors of bacterial protein synthesis

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S rRNA of the 30S subunit in the bacterial 70S ribosome.Mechanism of Ribosomal Disruption&#160; High-resolution structural studies have elucidated that aminoglycosides bind within the decoding center of the 30S subunit, particularly around helix 44 of 16S rRNA. Critical nucleotides involved in this interaction include A1408, A1492, and A1493. Upon drug binding, these residues undergo conformational changes that stabilize an aberrant flipped-out state, even in the presence of near-cognate tRNAs. This misregulation permits incorrect codon-anticodon pairing, resulting in the incorporation of erroneous amino acids into nascent peptides and the generation of misfolded, dysfunctional proteins.Interference with Translation and Ribosome Dynamics Beyond inducing translational errors, certain aminoglycosides such as streptomycin interfere with the formation of a functional initiation complex, hinder subunit joining, and impede elongation by affecting EF-G-mediated translocation. Ribosome recycling is also compromised as some aminoglycosides inhibit the concerted actions of RRF and EF-G required to dissociate the 70S complex. This culminates in ribosome stalling and sequestration of translational machinery.Cytotoxic Consequences and Resistance&#160; The downstream effects include the misintegration of aberrant membrane proteins, leading to compromised membrane integrity, ion leakage, and collapse of the proton motive force and ATP levels. These disruptions culminate in cell death, distinguishing aminoglycosides from bacteriostatic agents. Resistance mechanisms have evolved, including enzymatic drug modification, target methylation, ribosomal mutations, and reduced drug uptake. Detailed structural insights continue to inform the development of next-generation ribosome-targeting antibiotics.

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

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JoVE Core

Microbiology

Unit

Antimicrobial Agents

KEY TERMS AND CONCEPTS

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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