Trio Act of Boronolectin with Antibiotic-Metal Complexed Macromolecules toward Broad-Spectrum Antimicrobial Efficacy

• Published in: ACS infectious diseases 2017-11, Vol.3 (11), p.845-853
• Main Authors: Yang, Peng, Bam, Marpe, Pageni, Parasmani, Zhu, Tianyu, Chen, Yung Pin, Nagarkatti, Mitzi, Decho, Alan W, Tang, Chuanbing
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Apoptosis - drug effects; Bacteria - drug effects; Boron Compounds - pharmacology; Cells, Cultured; Female; Macromolecular Substances - chemistry; Macromolecular Substances - pharmacology; Metals - chemistry; Metals - pharmacology; Mice; Mice, Inbred C57BL; Microbial Viability - drug effects; Molecular Structure; Monosaccharides - pharmacology; Polymers; Spleen - cytology
• ISSN: 2373-8227; 2373-8227
• DOI: 10.1021/acsinfecdis.7b00132

Bacterial infections, particularly by Gram-negative pathogens, have become a serious threat to global healthcare due to the diminishing effectiveness of existing antibiotics. We report a nontraditional therapy to combine three components in one macromolecular system, in which boronic acid adheres to peptidoglycan or lipopolysaccharide via boron-polyol based boronolectin chemistry, cationic metal polymer frameworks interact with negatively charged cell membranes, and β-lactam antibiotics are reinstated with enhanced vitality to attack bacteria via evading the detrimental enzyme-catalyzed hydrolysis. These macromolecular systems exhibited high efficacy in combating pathogenic bacteria, especially Gram-negative strains, due to synergistic effects of multicomponents on interactions with bacterial cells. In vitro and in vivo cytotoxicity and hemolysis evaluation indicated that these multifunctional copolymers did not induce cell death by apoptosis, as well as did not alter the phenotypes of immune cells and did not show observable toxic effect on red blood cells.