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

Streptomisin gibi aminoglikozitler güçlü bakterisit antibiyotiklerdir. Bu antibiyotikler bakteriyel ribozomu hedef alır ve protein sentezini çeşitli şekillerde olumsuz etkiler.Streptomisin genellikle bakteriyel ribozomun 30S alt birimine bağlanır.Bu bağlanma, mRNA ile başlatıcı tRNA'nın doğru hizalanmasını engelleyen konformasyonel bozulmaya neden olur.Bu bozulma, fonksiyonel 70S başlatma kompleksinin oluşmasını daha da engeller.Sonuç olarak, ribozomlar işlevsel olmayan bir girişim öncesi durumda tutulmuş halde kalır.Streptomisin, uzalma aşamasında ribozomları da etkileyebilir. Ribozomun mRNA kodonlarını yanlış okuymasına ve yanlış amino asitler eklemesine neden olabilir.Bu translasyon hataları, bakteriyel hücre zarına yerleşebilen yanlış katlanmış veya kesilen proteinlere yol açar; bu proteinler hücrenin geçirgenliğini değiştirir ve hücre ölümüne yol açar.Ayrıca, streptomisin, ribozomları uzamayarak inaktif bir konformasyonda kilitleyebilir. Uzamayı durdurur ve çeviri sonlandırmasından sonra ribozomun geri dönüşümünü engeller.

bakteriyel protein sentezi inhibitörleri

Inhibitors of Bacterial Protein Synthesis

Aminoglikozidler, bakteriyel ribozomu hedef alarak, özellikle protein sentezini bozarak antimikrobiyal etkilerini gösteren son derece güçlü bir bakterisisit antibiyotik sınıfıdır. Bu polikasyonik moleküller, glikozidik bağlar aracılığıyla 2-deoksistreptamin veya streptamin gibi bir aminosiklitol çekirdeğe bağlı amino-modifiye şekerlerden oluşur. Güçlü pozitif yükleri, öncelikle bakteriyel 70S ribozomdaki 30S alt biriminin 16S rRNA'sında, ribozomal RNA'nın (rRNA) negatif yüklü fosfat omurgasına sıkı bağlanmayı kolaylaştırır.Ribozomal Bozulmanın Mekanizması Yüksek çözünürlüklü yapısal çalışmalar, aminoglikozitlerin 30S alt biriminin kod çözme merkezinde, özellikle 16S rRNA'nın heliks 44 etrafında bağlandığını ortaya koymuştur. Bu etkileşimde yer alan kritik nükleotidler arasında A1408, A1492 ve A1493 bulunur. İlaç bağlandığında, bu kalıntılar konformasyonel değişikliklere uğrar ve neredeyse benzer tRNA'lar olsa bile, anormal bir ters çevrilmiş durumu stabilize eder. Bu yanlış düzenleme, yanlış kodon-antikodon eşleşmesine yol açar ve yanlış aminli amino asitlerin yeni başlayan peptidlere dahil edilmesine ve yanlış katlanmış, işlevsiz proteinlerin oluşmasına yol açar.Çeviri ve Ribozom Dinamikleriyle Etkileşim Translasyon hatalarının yanı sıra, streptomisin gibi bazı aminoglikozidler fonksiyonel başlatma kompleksinin oluşumunu engeller, alt birim birleşmesini engeller ve EF-G aracılı translokasyonu etkilerek uzamayı engeller. Ribozom geri dönüşümü de bazı aminoglikozidlerin 70S kompleksini dissosiyasyon için gerekli RRF ve EF-G'nin uyumlu etkilerini inhibe etmesi nedeniyle zayıflamaktadır. Bu, ribozomun durması ve çeviri makinelerinin tutulmasıyla sonuçlanır.Sitotoksik Sonuçlar ve Direnç Sonraki etkiler arasında, anormal zar proteinlerinin yanlış entegrasyonu, zar bütünlüğünün bozulması, iyon sızıntısı ve proton hareket gücü ile ATP seviyelerinin çökmesi yer alır. Bu bozulmalar hücre ölümüne dönüşür ve aminoglikozidleri bakteriyostatik ajanlardan ayırır. Direnç mekanizmaları evrimleşmiştir; bunlar arasında enzimatik ilaç modifikasyonu, hedef metilasyon, ribozomal mutasyonlar ve azalmış ilaç alımı yer almaktadır. Ayrıntılı yapısal bilgiler, yeni nesil ribozom hedefleyen antibiyotiklerin geliştirilmesini bilgilendirmeye devam etmektedir.

Bakteriyel Protein Sentezi Inhibitörleri

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

Mikrobiyoloji

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Antimicrobial Agents

Antimikrobiyal Ajanlar

KEY TERMS AND CONCEPTS

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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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