A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action

Bai, Silei1,2,3; Wang, Jianxue1,2,3; Yang, Kailing1,2,4; Zhou, Calling1,2,4; Xu, Yangfan1,2,4; Song, Junfeng1,2,3; Gu, Yuanxin1,2,3; Chen, Zheng1,2,3; Wang, Min1,2,3; Shoen, Carolyn5; Andrade, Brenda6; Cynamon, Michael5; Zhou, Kai7,8; Wang, Hui9; Cai, Qingyun3; Oldfield, Eric6; Zimmerman, Steven C.6; Bai, Yugang1,2,3; Feng, Xinxin1,2,3

2021

10.1126/sciadv.abc9917

Science Advances   影响因子和分区

2375-2548

Antibiotic resistance is now a major threat to human health, and one approach to combating this threat is to develop resistance-resistant antibiotics. Synthetic antimicrobial polymers are generally resistance resistant, having good activity with low resistance rates but usually with low therapeutic indices. Here, we report our solution to this problem by introducing dual-selective mechanisms of action to a short amidine-rich polymer, which can simultaneously disrupt bacterial membranes and bind to bacterial DNA. The oligoamidine shows unobservable resistance generation but high therapeutic indices against many bacterial types, such as ESKAPE strains and clinical isolates resistant to multiple drugs, including colistin. The oligomer exhibited excellent effectiveness in various model systems, killing extracellular or intracellular bacteria in the presence of mammalian cells, removing all bacteria from Caenorhabditis elegans, and rescuing mice with severe infections. This "dual mechanisms of action" approach may be a general strategy for future development of antimicrobial polymers.

SCI ; EI

英语

NI期刊

其他

National Natural Science Foundation of China[21877033,21807031] ; U.S. NIH["R01GM065307","R01CA158191","R01AR069645"]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000614004600016

AMER ASSOC ADVANCEMENT SCIENCE

Web of Science

1.Hunan Univ, Inst Chem Biol & Nanomed, Changsha 410082, Hunan, Peoples R China
2.Hunan Univ, State Key Lab Chem Biosensing & Chemometr, Hunan Prov Key Lab Biomacromol Chem Biol, Changsha 410082, Hunan, Peoples R China
3.Hunan Univ, Sch Chem & Chem Engn, Changsha 410082, Hunan, Peoples R China
4.Hunan Univ, Sch Biol, Changsha 410082, Hunan, Peoples R China
5.Vet Affairs Med Ctr, Syracuse, NY 13210 USA
6.Univ Illinois, Dept Chem, Urbana, IL 61801 USA
7.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen Inst Resp Dis, Shenzhen 518035, Guangdong, Peoples R China
8.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China
9.Peking Univ Peoples Hosp, Dept Clin Labs, Beijing 100044, Peoples R China

Bai, Silei,Wang, Jianxue,Yang, Kailing,et al. A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action[J]. Science Advances,2021,7(5).

Bai, Silei.,Wang, Jianxue.,Yang, Kailing.,Zhou, Calling.,Xu, Yangfan.,...&Feng, Xinxin.(2021).A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action.Science Advances,7(5).

Bai, Silei,et al."A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action".Science Advances 7.5(2021).