Enhanced Synergistic Antibacterial and Antibiofilm Efficacy of Main-Chain Polysulfoniums with Antibiotics by Balancing Charge Density and Amphiphilicity

• Published in: ACS applied polymer materials Vol. 5; no. 6; pp. 4437 - 4447
• Main Authors: Zhao, Yao, Wang, Xiao, Hu, Yongjin, Zhao, Jinghua, Sun, Mei, Yang, Mingdi, Xuan, Han, Wang, Xianbiao, Zhang, Jingyan, Zhu, Zhiyuan, Rao, Jingyi
• Format: Journal Article
• Language: English
• Published: American Chemical Society 09.06.2023
• Subjects: combinational therapy; synergy effect; antibacterial; polysulfoniums; antibiofilm
• ISSN: 2637-6105; 2637-6105
• DOI: 10.1021/acsapm.3c00572

Infection diseases caused by Gram-negative pathogens are exceedingly difficult to treat because their characteristic outer membrane limits antibiotic entry. Herein, we report the development of main-chain polysulfoniums with different charge densities and amphiphilicities based on the quantitative methylation reaction. By regulating the membrane-disruption capability, the combined efficacy of polysulfoniums and antibiotic rifampicin can be manipulated from no interaction to synergy against Gram-negative bacteria Escherichia coli. After incubating with synergistic polysulfoniums/rifampicin combinations at a minimum inhibitory concentration (MIC), the time needed to achieve a 6-log reduction of E. coli can be accelerated 8 times compared to the antibiotic treatment. At 1/2 MIC, polysulfoniums/rifampicin combinations can provide a 90% reduction in biofilm mass and 8-log orders of embedded bacteria killing in 3-day-mature E. coli biofilms. This work demonstrates that alkylation chemistry can serve as a reliable means to create antibiotic adjuvants in combating infections caused by Gram-negative pathogens and biofilms.