Multi-armed antibiotics for Gram-positive bacteria

Jia，Yuexiao1,3; Chen，Wenwen2; Tang，Rongbing1; Zhang，Jiangjiang1; Liu，Xiaoyan1; Dong，Ruihua1; Hu，Fupin4; Jiang，Xingyu1

2023-07-12

10.1016/j.chom.2023.06.008

Cell Host and Microbe   影响因子和分区

1931-3128

1934-6069

Antibiotic resistance is a serious threat to public health. Here, we propose a multi-armed chemical scaffold (MACS) for antibiotic screening, which refers to multi-armed molecules (MAMs) consisting of a core unit and three or four arms, neither of which is active for pathogens. Based on a structure-activity relationship study of MAMs, we discover a class of multi-armed antibiotics (MAAs) with a core similar to ethylene (E), carbon atom (C), benzene (B), nitrogen atom (N), and triazine (T) and three or four 4-phenylbenzoic acid (PBA) arms, or a B core and three 4-vinylbenzoic acid (VBA) or 4-ethynylbenzoic acid (EBA) arms. They can selectively interact with Gram-positive bacteria and inhibit cell wall assembly by targeting the lipid carriers of cell wall biosynthesis. MAAs have excellent antibacterial activities against Gram-positive bacteria, including clinical multi-drug-resistant (MDR) isolates. Our study provides a chemical scaffold and identifies eight antibacterial lead compounds for the development of antibiotics.

antibiotics cell wall assembly low risk of resistance multi-drug resistant bacteria

SCI

英语

NI论文

第一 ; 通讯

Guangdong Innovative and Entrepreneurial Research Team Program[2019ZT08Y191];China Postdoctoral Science Foundation[2020M671886];National Natural Science Foundation of China[21535001];National Natural Science Foundation of China[22074094];National Natural Science Foundation of China[22104049];National Natural Science Foundation of China[22234004];

Microbiology ; Parasitology ; Virology

Microbiology ; Parasitology ; Virology

WOS:001044507800001

CELL PRESS

2-s2.0-85164359452

Scopus

1.Shenzhen Key Laboratory of Smart Healthcare Engineering,Guangdong Provincial Key Laboratory of Advanced Biomaterials,Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,No. 1088 Xueyuan Rd., Nanshan District, Guangdong,518055,China
2.School of Biomedical Engineering,Shenzhen University Medical School,Shenzhen University,Shenzhen,Guangdong,518055,China
3.Institute of Biomedical Engineering and Health Sciences,School of Medical and Health Engineering,Changzhou University,Changzhou,Jiangsu,213164,China
4.Institute of Antibiotics,Huashan Hospital,Fudan University,Shanghai,200040,China

Jia，Yuexiao,Chen，Wenwen,Tang，Rongbing,et al. Multi-armed antibiotics for Gram-positive bacteria[J]. Cell Host and Microbe,2023,31(7):1101-1110.e5.

Jia，Yuexiao.,Chen，Wenwen.,Tang，Rongbing.,Zhang，Jiangjiang.,Liu，Xiaoyan.,...&Jiang，Xingyu.(2023).Multi-armed antibiotics for Gram-positive bacteria.Cell Host and Microbe,31(7),1101-1110.e5.

Jia，Yuexiao,et al."Multi-armed antibiotics for Gram-positive bacteria".Cell Host and Microbe 31.7(2023):1101-1110.e5.