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

스트렙토마이신과 같은 아미노글리코사이드는 강력한 박테리아 살해 항생제입니다. 이 항생제들은 박테리아 리보솜을 표적으로 하여 단백질 합성을 여러 방식으로 저해합니다.스트렙토마이신은 일반적으로 박테리아 리보솜의 30S 소단위에 결합합니다.이 결합은 구조 왜곡을 일으켜 mRNA와 시작자 tRNA의 올바른 정렬을 방해합니다.이 왜곡은 기능적 70S 개시 복합체의 형성을 더욱 방해합니다.그 결과, 리보솜은 기능 장애 전 단계에 머무른 상태로 남아 있습니다.스트렙토마이신은 신장 단계에서 리보솜에도 영향을 줄 수 있습니다. 이로 인해 리보솜이 mRNA 코돈을 잘못 읽어 잘못된 아미노산을 추가할 수 있습니다.이러한 번역 오류로 인해 단백질이 잘못 접히거나 절단되어 박테리아 세포막에 삽입되어 투과성을 변화시키고 세포 사멸로 이어집니다.또한, 스트렙토마이신은 비활성 구조에서 신장 과정에서 리보솜을 고정할 수 있습니다. 이는 연장을 멈추고 번역 종료 후 리보솜의 재활용을 방지합니다.

박테리아 단백질 합성 억제제

Inhibitors of Bacterial Protein Synthesis

아미노글리코사이드는 박테리아 리보솜을 표적으로 하여 단백질 합성을 방해함으로써 항균 효과를 발휘하는 매우 강력한 박테리아 살균성 항생제 계열을 이룹니다. 이 폴리양이온 분자는 2-디옥시스트렙타민이나 스트렙타민과 같은 아미노사이클리톨 코어에 당시디 결합을 통해 결합된 아미노 변형 당으로 구성되어 있습니다. 이들의 강한 양전하는 주로 박테리아 70S 리보솜의 30S 소단위체 16S rRNA에 음전하를 띤 인산염 골격에 밀착하는 것을 돕습니다.리보솜 붕괴의 기전 고해상도 구조 연구를 통해 아미노글리코사이드가 30S 소단위체의 해독 중심, 특히 16S rRNA의 44호 나선 부위에 결합한다는 것이 밝혀졌습니다. 이 상호작용에 관여하는 핵심 뉴클레오타이드로는 A1408, A1492, A1493이 있습니다. 약물 결합 시 이 잔기들은 구조 변화를 겪어 비정상적인 뒤집힌 상태를 안정화시키는데, 이는 거의 동일한 tRNA가 존재하는 경우에도 마찬가지입니다. 이 오조절은 잘못된 코돈-안티코돈 쌍을 허용하여 잘못된 아미노산이 초기 펩타이드에 포함되고 잘못 접히고 기능 장애가 있는 단백질을 생성하게 만듭니다.번역 및 리보솜 역학 간섭 번역 오류를 유발하는 것 외에도, 스트렙토마이신과 같은 특정 아미노글리코사이드는 기능적 개시 복합체 형성을 방해하고, 소단위체 결합을 방해하며, EF-G 매개 전위를 통해 신장을 방해합니다. 리보솜 재활용도 일부 아미노글리코사이드가 70S 복합체를 해리하는 데 필요한 RRF와 EF-G의 협력 작용을 억제하기 때문에 저해됩니다. 이는 리보솜 정체와 번역 기구의 격리로 절정에 이릅니다.세포독성 결과 및 내성 그 후반 효과로는 이상 막 단백질의 오통합이 포함되며, 이는 막 무결성 손상, 이온 누출, 양성자 동력과 ATP 수치의 붕괴로 이어집니다. 이러한 교란은 결국 세포 사멸로 이어지며, 아미노글리코사이드를 균 억제제와 구분합니다. 효소 약물 변형, 표적 메틸화, 리보솜 돌연변이, 약물 흡수 감소 등 내성 기전이 진화해 왔습니다. 상세한 구조적 통찰은 차세대 리보솜 표적 항생제 개발에 계속 기여하고 있습니다.

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

교육

JoVE Core

Microbiology

미생물학

Unit

단위

Antimicrobial Agents

항균제

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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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