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

Aminoglykoside, wie Streptomycin, sind wirksame bakterizide Antibiotika. Diese Antibiotika zielen auf das bakterielle Ribosom ab und beeinträchtigen die Proteinsynthese auf vielfältige Weise.Streptomycin bindet typischerweise an die 30S-Untereinheit des bakteriellen Ribosoms.Diese Bindung verursacht eine konformationelle Verzerrung, die die korrekte Ausrichtung von mRNA und Initiator-tRNA verhindert.Die Verzerrung verhindert zudem die Bildung des funktionalen 70S-Initiierungskomplexes.Infolgedessen bleiben die Ribosomen in einem nicht funktionsfähigen Zustand vor der Initiierung stillgelegt.Streptomycin kann während der Elongationsphase auch Ribosomen beeinflussen. Es kann dazu führen, dass das Ribosom mRNA-Codons falsch liest und falsche Aminosäuren hinzufügt.Diese Translationsfehler führen zu fehlgefalteten oder abgeschnittenen Proteinen, die sich in die bakterielle Zellmembran einfügen, deren Durchlässigkeit verändern und zum Zelltod führen.Außerdem kann Streptomycin die Ribosomen während der Verlängerung in einer inaktiven Konformation blockieren. Es stoppt die Verlängerung und verhindert das Recycling von Ribosomen nach dem Übersetzungstermin.

inhibitoren der bakteriellen proteinsynthese

Inhibitors of Bacterial Protein Synthesis

Aminoglykosiden bilden eine hochpotente Klasse bakterizider Antibiotika, die ihre antimikrobielle Wirkung entfalten, indem sie das bakterielle Ribosom angreifen und insbesondere die Proteinsynthese stören. Diese polykationischen Moleküle bestehen aus aminomodifizierten Zuckern, die durch glykosidische Bindungen an einen Aminocyclitolkern wie 2-Desoxystreptamin oder Streptamin gebunden sind. Ihre starken positiven Ladungen ermöglichen eine enge Bindung an das negativ geladene Phosphat-Rückgrat der ribosomalen RNA (rRNA), hauptsächlich an der 16S-rRNA der 30S-Untereinheit des bakteriellen 70S-Ribosoms.Mechanismus der ribosomalen Störung Hochauflösende strukturelle Studien haben gezeigt, dass Aminoglykosidee im Dekodierungszentrum der 30S-Untereinheit binden, insbesondere um die Helix 44 von 16S rRNA. Kritische Nukleotide, die an dieser Wechselwirkung beteiligt sind, sind A1408, A1492 und A1493. Bei der Arzneimittelbindung durchlaufen diese Rückstände konformationelle Veränderungen, die einen aberranten, ausgeflippten Zustand stabilisieren, selbst in Anwesenheit nahezu verwandter tRNAs. Diese Fehlregulation ermöglicht eine falsche Codon-Anticodon-Paarung, was zur Einbindung fehlerhafter Aminosäuren in entstehende Peptide und zur Bildung fehlgefalteter, dysfunktionaler Proteine führt.Interferenz mit Translation und Ribosomendynamik Neben der induzierten Translationsfehler beeinträchtigen bestimmte Aminoglykosiden wie Streptomycin die Bildung eines funktionellen Initiationskomplexes, behindern die Verbindung von Untereinheiten und behindern die Verlängerung, indem sie EF-G-vermittelte Translokation beeinflussen. Das Ribosomenrecycling ist ebenfalls beeinträchtigt, da einige Aminoglykosidee die konzertierten Wirkungen von RRF und EF-G hemmen, die zur Dissoziation des 70S-Komplexes erforderlich sind. Dies gipfelt in einer Ribosom-Verzögerung und Einlagerung translationaler Maschinen.Zytotoxische Folgen und Resistenz Die nachgelagerten Effekte umfassen die Fehlintegration abweichender Membranproteine, was zu einer Beeinträchtigung der Membranintegrität, Ionenlecks und einem Zusammenbruch der Protonenantriebskraft und ATP-Niveaus führt. Diese Störungen gipfeln im Zelltod, wodurch Aminoglykoside von bakteriostatischen Agenten unterschieden werden. Es haben sich Resistenzmechanismen entwickelt, darunter enzymatische Arzneimittelmodifikation, Zielmethylierung, ribosomale Mutationen und eine verminderte Medikamentenaufnahme. Detaillierte strukturelle Erkenntnisse informieren weiterhin die Entwicklung von ribosomorientierten Antibiotika der nächsten Generation.

Inhibitoren der bakteriellen Proteinsynthese

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

https://cloudfront.jove.com/files/ftp_upload/40860/40860_article_thumb_40860.jpg

inhibitors-of-bacterial-protein-synthesis

Education

Lehre

JoVE Core

Microbiology

Mikrobiologie

Unit

Einheit

Antimicrobial Agents

Antimikrobielle Wirkstoffe

KEY TERMS AND CONCEPTS

ZENTRALE BEGRIFFE UND KONZEPTE

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

inhibitors of gram-positive cell wall synthesis

inhibitors-of-gram-positive-cell-wall-synthesis

How Antibiotics Block Bacterial Cell Walls

Bacterial cell walls are rigid structures built mainly from peptidoglycan. This mesh-like polymer gives bacteria strength and helps maintain cell shape. Because peptidoglycan synthesis is essential for growth, it is a major target for antibiotics. Beta-lactam antibiotics, such as penicillin, stop peptidoglycan synthesis in actively growing cells. They have a four-membered beta-lactam ring that mimics the D-alanyl-D-alanine dipeptide, which is the natural substrate for transpeptidase, also...

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...

inhibitors of bacterial dna synthesis

Fluoroquinolone Antibiotics and Bacterial DNA

Fluoroquinolone antibiotics target bacterial DNA replication by blocking two key type II topoisomerases: DNA gyrase and topoisomerase IV. These enzymes help bacteria manage DNA supercoiling and separate chromosomes during replication. When they are disrupted, bacterial pathogens cannot copy DNA efficiently and infection can spread less effectively. Fluoroquinolones are synthetic versions of quinolones. They work by stabilizing the short-lived DNA-enzyme cleavage complex, which stops strand...

inhibitors of viral protein synthesis

Interferons Block Viral Replication

Interferons block viral replication by shutting down protein synthesis and activating the cell’s antiviral defenses. Viruses need the host cell’s translational machinery to make proteins, because they do not have the machinery to do this on their own. When a virus is detected, infected cells release interferons, which are cytokines, or signaling proteins, that warn nearby uninfected cells. Interferons bind to receptors on nearby cells and activate the JAK-STAT signaling pathway. This turns on...

inhibitors of virion release

Neuraminidase Inhibitors and Flu Spread

Influenza viruses spread when new virions leave an infected cell and reach nearby cells. Influenza A and B are negative-sense, single-stranded RNA viruses with segmented genomes. They depend on two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), to infect cells, make new viral particles, and release them. HA starts infection by binding to sialic acid on the surface of host epithelial cells. This binding helps the virus enter the cell by receptor-mediated endocytosis. After...

antiviral nucleoside inhibitors

How Antiviral Drugs Stop Viral Replication

Antiviral nucleoside inhibitors stop viruses by blocking DNA or RNA synthesis. These drugs are structural analogs, which means they look like natural nucleosides, the building blocks cells use to make genetic material. Because they resemble host nucleosides, they can interfere with viral polymerases and disrupt viral genome replication. Acyclovir is a guanosine analog with a three-carbon acyclic side chain. It mainly targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2...

antifungal agents

Amphotericin B and Fungal Membranes

Amphotericin B targets fungal cell membranes by binding to ergosterol, a sterol found mainly in fungal plasma membranes. Its amphipathic structure helps this selective binding. It has a hydrophobic polyene-lactone ring and a hydrophilic region with mycosamine and carboxylic acid groups. Weak binding to cholesterol can also affect human cells and helps explain the drug’s toxicity. One way amphotericin B kills fungi is through pore formation. In this model, amphotericin B-ergosterol complexes...

mechanism of antibiotic resistance in mrsa

mechanism-of-antibiotic-resistance-in-mrsa

How Bacteria Outsmart Antibiotics

Antibiotic resistance in bacteria happens when microbes evolve the ability to survive drugs that once killed them or slowed their growth. Genetic change and antibiotic exposure drive this process. Over time, useful treatments can stop working. Bacteria can resist antibiotics in several ways. Some make drug-inactivating enzymes, such as beta-lactamases. Others use efflux pumps to push antibiotics out of the cell. Resistance can also come from mutations that change the drug target, from lower...

anthelminthic agents

Helminth Drugs and How They Work

Helminth drugs work by attacking the weak points of parasitic worms. These anthelmintic medicines are different from drugs used against protozoa, because they are usually aimed at mature helminths rather than fast-dividing cells. They target the worm’s movement, glucose use, and microtubule structure to stop survival, reproduction, and location inside the host. Benzimidazoles are broad-spectrum anthelmintics that block tubulin polymerization, which means they interfere with microtubules, the...

clinical significance of antibiotic resistance

clinical-significance-of-antibiotic-resistance

MRSA: Host Adaptation and Transmission

MRSA, or methicillin-resistant Staphylococcus aureus, is a major public health threat. It resists beta-lactam antibiotics because it carries the mecA gene inside the staphylococcal cassette chromosome mec, or SCCmec. The mecA gene makes penicillin-binding protein 2a, which reduces how well methicillin and related beta-lactam drugs can bind. MRSA has spread into separate clonal lineages that affect both humans and animals. These lineages fit the One Health idea, which links human, animal, and...

inhibitors of virion maturation and assembly

inhibitors-of-virion-maturation-and-assembly

HIV Protease Inhibitors and Maturation

HIV protease inhibitors block a key step in virus maturation. In human immunodeficiency virus (HIV), infected cells make two long precursor proteins called polyproteins. These are Gag and Gag-Pol. Gag provides the virus structure. Gag-Pol carries important viral enzymes, including reverse transcriptase, integrase, and protease. After these polyproteins are made, they move to the host cell membrane. There, they help build an immature viral particle that buds from the cell surface. Budding...

antiprotozoal agents

Leishmaniasis and Trypanothione Reductase

Leishmaniasis is a parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. Treatment often relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. The way these drugs work has not been fully clear. One important target is trypanothione reductase, or TR, an enzyme that helps keep Leishmania in redox balance. TR is not found in mammalian hosts, so it is a...

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

Description

Transcript

Tags