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

Aminoglikozydy, takie jak streptomycyna, są silnymi antybiotykami bakteriobójczymi. Te antybiotyki celują w rybosom bakteryjne, upośledzając syntezę białek na wiele sposobów.Streptomycyna zazwyczaj wiąże się z podjednostką 30S rybosomu bakteryjnego.To wiązanie powoduje zniekształcenie konformacyjne, uniemożliwiając prawidłowe ustawienie mRNA i inicjatora tRNA.Zniekształcenie dodatkowo uniemożliwia powstanie funkcjonalnego kompleksu inicjacyjnego 70S.W rezultacie rybosomy pozostają zatrzymane w niefunkcjonalnym stanie przedinicjacyjnym.Streptomycyna może również wpływać na rybosomy podczas fazy wydłużania. Może to powodować, że rybosom błędnie odczytuje kodony mRNA i dodaje niewłaściwe aminokwasy.Te błędy translacyjne powodują nieprawidłowo fałdowane lub ścięte białka, które mogą włożyć się w błonę komórkową bakteryjną, zmieniając jej przepuszczalność i prowadząc do śmierci komórki.Dodatkowo, streptomycyna może blokować rybosomy podczas wydłużania w nieaktywnej konformacji. Zatrzymuje wydłużenie i zapobiega recyklingowi rybosomów po zakończeniu translacji.

inhibitory syntezy białek bakteryjnych

Inhibitors of Bacterial Protein Synthesis

Aminoglikozydy stanowią wysoce silną klasę bakteriobójczych antybiotyków, które wywierają swoje działanie przeciwdrobnoustrojowe poprzez celowanie w bakteryjne rybosom, a w szczególności zakłócają syntezę białek. Te polimerowe cząsteczki składają się z aminomodyfikowanych cukrów połączonych wiązaniami glikozydowymi z rdzeniem aminocyklitolowym, takim jak 2-deoksystreptamina lub streptamina. Ich silne ładunki dodatnie ułatwiają ścisłe wiązanie z ujemnie naładowanym szkieletem fosforanowym RNA rybosomalnego (rRNA), głównie w 16S rRNA podjednostki 30S w rybosomie bakteryjnym 70S.Mechanizm zakłóceń rybosomalnych Badania strukturalne o wysokiej rozdzielczości wykazały, że aminoglikozydy wiążą się w centrum dekodującym podjednostki 30S, szczególnie wokół helisy 44 rRNA 16S. Krytyczne nukleotydy zaangażowane w tę interakcję to A1408, A1492 i A1493. Po wiązaniu leku te reszty ulegają zmianom konformacyjnym, które stabilizują aberrancki stan odwrócony, nawet w obecności niemal pokrewnych tRNA. Ta nieprawidłowa regulacja pozwala na nieprawidłowe parowanie kodon z antykodonem, co prowadzi do włączenia błędnych aminokwasów do powstających peptydów i powstawania źle złożonych, dysfunkcyjnych białek.Zakłócenia w translacji i dynamice rybosomów Poza wywoływaniem błędów translacyjnych, niektóre aminoglikozydy, takie jak streptomycyna, zakłócają tworzenie funkcjonalnego kompleksu inicjacyjnego, utrudniają łączenie podjednostek i hamują wydłużenie, wpływając na translokację pośredniczoną przez EF-G. Recykling rybosomów jest również osłabiony, ponieważ niektóre aminoglikozydy hamują skoordynowane działania RRF i EF-G niezbędne do dysocjacji kompleksu 70S. To prowadzi do zatrzymania rybosomów i sekwestracji mechanizmów translacyjnych.Konsekwencje cytotoksyczne i odporność Dalsze skutki obejmują niewłaściwą integrację aberrancyjnych białek błonowych, prowadzącą do jej osłabienia, wycieku jonów oraz załamania siły napędowej protonu i poziomu ATP. Te zaburzenia kończą się śmiercią komórek, co odróżnia aminoglikozydy od czynników bakteriostatycznych. Mechanizmy oporności ewoluowały, w tym modyfikacje enzymatyczne leków, metylacja celowa, mutacje rybosomowe oraz zmniejszone pobieranie leków. Szczegółowe analizy strukturalne nadal wspierają rozwój nowej generacji antybiotyków celujących w rybosomy.

Inhibitory syntezy białek bakteryjnych

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

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Microbiology

Mikrobiologia

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Antimicrobial Agents

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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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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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