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

الأمينوجليكوسيدات مثل الستربتومايسين هي مضادات حيوية قوية لمكافحة البكتيريا. تستهدف هذه المضادات الحيوية الريبوسوم البكتيري، مما يعيق تخليق البروتين بطرق متعددة.عادة ما يرتبط الستربتوميسين بوحدة 30S من الريبوسوم البكتيري.يسبب هذا الارتباط تشوها شكليا، مما يمنع المحاذاة الصحيحة لل mRNA وtRNA المبدئ.يمنع التشويه أيضا تكوين مركب البدء الوظيفي 70S.ونتيجة لذلك، تبقى الريبوسومات معلقة في حالة غير وظيفية قبل بدء العمل.يمكن أن يؤثر الستربتوميسين أيضا على الريبوسومات خلال مرحلة الإطالة. يمكن أن يتسبب في خطأ قراءة كودونات mRNA للريبوسوم وإضافة أحماض أمينية خاطئة.تؤدي هذه الأخطاء الانتقالية إلى بروتينات غير مطوية أو مقطوعة يمكن أن تدخل إلى غراء الخلية البكتيرية، مما يغير نفاذيته ويؤدي إلى موت الخلية.بالإضافة إلى ذلك، يمكن للستربتوميسين أن يحبس الريبوسومات أثناء الاستطالة في شكل غير نشط. يوقف الإطالة ويمنع إعادة تدوير الريبوسوم بعد انتهاء الترجمة.

مثبطات تخليق البروتينات البكتيرية

Inhibitors of Bacterial Protein Synthesis

تشكل الأمينوجليكوسيدات فئة قوية جدا من المضادات الحيوية الباكتيرية التي تمارس تأثيراتها المضادة للميكروبات من خلال استهداف الريبوسوم البكتيري، وبشكل خاص مما يعطل تخليق البروتين. تتكون هذه الجزيئات متعددة البكاتوشيات من سكريات معدلة أمينو-معدلة مرتبطة عبر روابط جليكوزيدية بنواة أمينوسيكليتول مثل 2-ديوكسيستريبتامين أو ستربتامين. تسهل شحناتها الإيجابية القوية الارتباط بإحكام بالعمود الفقري للفوسفات سالب الشحنة في الحمض النووي الريبوزومي (rRNA)، خاصة عند 16S rRNA للوحدة الفرعية 30S في ريبوسوم 70S البكتيري.آلية الاضطراب الريبوسومي أوضحت الدراسات الهيكلية عالية الدقة أن الأمينوجليكوسيدات ترتبط داخل مركز فك التشفير في وحدة 30S، خاصة حول الحلزون 44 من 16S rRNA. تشمل النيوكليوتيدات الحرجة المشاركة في هذا التفاعل A1408 وA1492 وA1493. عند الارتباط بالأدوية، تخضع هذه البقايا لتغيرات شكلية تثبت حالة انعكاسية شاذة، حتى في وجود tRNA شبه متشابه. يسمح هذا التنظيم الخاطئ باقتران غير صحيح بين الكودون ومضاد الكودونات، مما يؤدي إلى دمج الأحماض الأمينية الخاطئة في الببتيدات الناشئة وإنتاج بروتينات غير مطوية وغير وظيفية.التداخل مع الترجمة وديناميكيات الريبوسوم بعيدا عن تحفيز الأخطاء الترجمية، تتداخل بعض الأمينوجليكوسيدات مثل الستربتومايسين مع تكوين مركب بدء وظيفي، وتعيق الربط بين الوحدات الفرعية، وتعيق الإطالة من خلال التأثير على النقل الناتج عن EF-G. كما أن إعادة تدوير الريبوسوم تتأثر أيضا حيث أن بعض الأمينوجليكوسيدات تثبط التأثيرات المنسقة ل RRF وEF-G اللازمة لتفكيك مركب السبعينيات. يتوج ذلك في توقف الآلات التحويلية واحتجاز الريبوسوم.العواقب السامة للخلايا والمقاومة تشمل التأثيرات اللاحقة اختلاط اندماج بروتينات الغشاء الشاذة، مما يؤدي إلى تضرر في سلامة الغشاء، وتسرب الأيونات، وانهيار قوة الدفع والبروتون ومستويات ATP. تبلغ هذه الاضطرابات ذروتها في موت الخلايا، مما يميز الأمينوجليكوسيدات عن العوامل البكتيريوستاتيكية. تطورت آليات المقاومة، بما في ذلك تعديل الأدوية الإنزيمي، والميثلة المستهدفة، والطفرات الريبوسومية، وتقليل امتصاص الأدوية. تستمر الرؤى الهيكلية التفصيلية في تطوير الجيل القادم من المضادات الحيوية المستهدفة للريبوسومات.

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

JoVE Core

Microbiology

علم الأحياء الدقيقة

Unit

وحدة

Antimicrobial Agents

العوامل المضادة للميكروبات

KEY TERMS AND CONCEPTS

المصطلحات والمفاهيم الأساسية

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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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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