한빛사논문
- 조회527
Eun Young Kim a,1, S. Dinesh Kumar a,1, Jeong Kyu Bang b,1, Chelladurai Ajish a, Sungtae Yang c, Byambasuren Ganbaatar d, Jeongeun Kim d, Chul Won Lee d, Sung‑Jin Cho e, Song Yub Shin a
aDepartment of Cellular & Molecular Medicine, School of Medicine, Chosun University, Gwangju 61452, Republic of Korea
bDivision of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang 28119, Chung Buk, Republic of Korea
cDepartment of Microbiology, School of Medicine, Chosun University, Gwangju 61452, Republic of Korea.
dDepartment of Chemistry, Chonnam National University, Gwangju 61186, Republic of Korea.
eDepartment of Biological Sciences and Biotechnology, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea
1These authors contributed equally to this work.
Corresponding authors: Sung‑Jin Cho, Song Yub Shin
Abstract
We recently designed a series of cationic deoxythymidine-based amphiphiles that mimic the cationic amphipathic structure of antimicrobial peptides (AMPs). Among these amphiphiles, ADG-2e and ADL-3e displayed the highest selectivity against bacterial cells. In this study, ADG-2e and ADL-3e were evaluated for their potential as novel classes of antimicrobial, antibiofilm, and anti-inflammatory agents. ADG-2e and ADL-3e showed good resistance to physiological salts and human serum, and a low incidence of drug resistance. Moreover, they exhibit proteolytic resistance against pepsin, trypsin, α-chymotrypsin, and proteinase K. The antimicrobial mechanism of ADG-2e and ADL-3e was investigated by membrane depolarization, cell membrane integrity analysis, scanning electron microscopy (SEM), genomic DNA influence and genomic DNA binding assay. ADG-2e and ADL-3e were found to kill bacteria by an intracellular target mechanism and bacterial cell membrane-disrupting mechanism, respectively. Furthermore, ADG-2e and ADL-3e showed effective synergistic effects when combined with several conventional antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Importantly, ADG-2e and ADL-3e not only suppressed MDRPA biofilm formation but also effectively eradicated mature MDRPA biofilms. Furthermore, ADG-2e and ADL-3e drastically decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) gene expression and protein secretion in lipopolysaccharide (LPS)-stimulated macrophages, implying potent anti-inflammatory activity in LPS-induced inflammation. Our findings suggest that ADG-2e and ADL-3e could be further developed as novel antimicrobial, antibiofilm, and anti-inflammatory agents to combat bacterial infections.
논문정보
- Research article
- 2023년 07월 (BRIC 등록일 2023-07-25)
- 국내 연구진
- 의약학 > 분자세포의학
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