미생물 항생제어 실험실

항생제 내성균주의 출현은 항생제의 사용을 제한하여 병원성 세균 감염의 임상적 치료에 중요한 위협이 된다 . 현재 치료의 마지막 수단으로 간주되고 있는 반코마이신에 대한 내성 병원성 박테리아가 매우 광범위하게 발견되고 있기 때문에 새로운 항생제 개발에 대한 요구가 증가하고 있다 . 따라서 기존의 RNA 및 DNA 합성과 같은 세포 내 주요 생합성 과정을 저해하는 항생제들이 사용되고 있지만 , 본 실험실에서는 새로운 항생제 타겟을 발굴하고 선별하여 이에 대한 신개념 항생제를 개발하는 것을 목표로 한다 .

대부분의 항생제는 리보솜의 기능을 억제하여 단백질 합성을 저해한다 . 따라서 본 실험실에서는 리보솜 합성에 직접적으로 관여하는 단백질을 저해하여 단백질 합성을 억제하고 세포생장을 제어하고자 한다 . 이를 위해 50S, 30S 리보솜 생합성에 관여하는 GTPase 들을 발굴하고 기능적 연구를 하여 이에 대한 항생제 선도물질을 선별하고자 한다 .

The emergence of antibiotics-resistant bacterial strains is a major threat to the clinical treatment of pathogenic bacterial infections, which limits the use of currently available antibiotics. Vancomycin-resistant pathogenic bacteria are now quite widely found. As vancomycin is considered to be the last resort in the present treatment of drug-resistant bacterial infections, development of new potent antibiotics has become extremely demanding. Antibiotics such as penicillin target bacterial cell wall biosynthesis, and some antibiotics, such as kanamycin, streptomycin and tetracycline, inhibit protein synthesis. Cellular processes such as RNA and DNA synthesis are interrupted by rifampicin and novomycin, respectively. These currently available conventional antibiotics target various macromolecular biosynthetic systems in the bacteria described above, as they are unique in bacterial cells or distinct from those in eukaryotic cells. While the screening of new antibiotics against macromolecular biosynthesis targets is ongoing, the alarming pace of the development of drug resistance has created the urgent need for the search for non-conventional antibacterial targets.

Bacterial ribosome consists of three rRNAs and 55 ribosomal proteins as a macromolecular complex, which, in turn, 16S rRNA and 21 proteins form 30S subunit and 5S, 23S and 34 proteins form 50S subunit. In order to understand the intracellular synthesis of ribosome, many studies have been done in vitro to explore the temporal and spatial synthesis of the ribosome, however, so far, the efficient intracellular biogenesis of ribosome is not clear. It was believed that all information for the effective synthesis is embedded in the primary structure of rRNAs and ribosomal proteins. Recent researches revealed that in addition to rRNAs and ribosomal proteins, helicases, chaperones, and modification of rRNAs and ribosomal proteins play an essential role in ribosome synthesis. Among them, bacterial GTPases are known to be involved in the biosynthesis of the ribosome.

In our laboratory, we study non-ribosomal ribosome assembly proteins, especially, bacterial GTPases in an attempt to develop novel antibiotics against them. Thus, by inhibiting the activity of GTPases, ribosome biosynthesis and translation will affect bacterial growth.