Facial amphiphilic naphthoic acid-derived antimicrobial polymers against multi-drug resistant gram-negative bacteria and biofilms.
Leman Buzoglu Kurnaz, Swagatam Barman, Xiaoming Yang, Claire Fisher, F Wayne Outten, Prakash Nagarkatti, Mitzi Nagarkatti, Chuanbing Tang
Author Information
Leman Buzoglu Kurnaz: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, United States.
Swagatam Barman: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, United States.
Xiaoming Yang: Department of Pathology, Microbiology and Immunology, University of South Carolina, School of Medicine, Columbia, SC, 29209, United States.
Claire Fisher: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, United States.
F Wayne Outten: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, United States.
Prakash Nagarkatti: Department of Pathology, Microbiology and Immunology, University of South Carolina, School of Medicine, Columbia, SC, 29209, United States.
Mitzi Nagarkatti: Department of Pathology, Microbiology and Immunology, University of South Carolina, School of Medicine, Columbia, SC, 29209, United States.
Chuanbing Tang: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, United States. Electronic address: tang4@mailbox.sc.edu.
Inspired by the facial amphiphilic nature and antimicrobial efficacy of many antimicrobial peptides, this work reported facial amphiphilic bicyclic naphthoic acid derivatives with different ratios of charges to rings that were installed onto side chains of poly(glycidyl methacrylate). Six quaternary ammonium-charged (QAC) polymers were prepared to investigate the structure-activity relationship. These QAC polymers displayed potent antibacterial activity against various multi-drug resistant (MDR) gram-negative pathogens such as Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Polymers demonstrated low hemolysis and high antimicrobial selectivity. Additionally, they were able to eradicate established biofilms and kill metabolically inactive dormant cells. The membrane permeabilization and depolarization results indicated a mechanism of action through membrane disruption. Two lead polymers showed no resistance from MDR-P. aeruginosa and MDR-K. pneumoniae. These facial amphiphiles are potentially a new class of potent antimicrobial agents to tackle the antimicrobial resistance for both planktonic and biofilm-related infections.
