한빛사논문
- 조회367
성균관대학교
Ji-Hoon Kim1, Yunmi Lee2, Inseo Kim1, JuOae Chang1, Subin Hong1, Na Kyung Lee3, David Shum3, Seongeun Baek4, Wooseong Kim4, Soojin Jang,2* and Wonsik Lee1*
1School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
2Antibacterial Resistance Laboratory, Institut Pasteur Korea, Seongnam13488, Republic of Korea
3Screening Discovery Platform, Institut Pasteur Korea, Seongnam13488, Republic of Korea
4College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
CORRESPONDING AUTHORS: Soojin Jang, Wonsik Lee
Abstract
Small molecule can be utilized to restore the effectiveness of existing major classes of antibiotics against antibiotic-resistant bacteria. In this study, it is demonstrated that celastrol, a natural compound, can modify the bacterial cell wall and subsequently render bacteria more suceptible to β-lactam antibiotics. It is shown that celastrol leads to incomplete cell wall crosslinking by modulating levels of c-di-AMP, a secondary messenger, in methicillin-resistant Staphylococcus aureus (MRSA). This mechanism enables celastrol to act as a potentiator, effectively rendering MRSA susceptible to a range of penicillins and cephalosporins. Restoration of in vivo susceptibility of MRSA to methicillin is also demonstrated using a sepsis animal model by co-administering methicillin along with celastrol at a much lower amount than that of methicillin. The results suggest a novel approach for developing potentiators for major classes of antibiotics by exploring molecules that re-program metabolic pathways to reverse β-lactam-resistant strains to susceptible strains.
논문정보
- Research article
- 2024년 05월 (BRIC 등록일 2024-05-16)
- 국내 연구진
- 생명과학 > 미생물학
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