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Hydrophilic and cationic polymers as potent antimicrobial materials: another pathway to fight tough bacterial infections
Jiang, Yunjiang
Jiang, Yunjiang
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2015
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2016-06-01
Abstract
Membrane-active antimicrobial peptides and their synthetic mimics have been studied extensively as a new generation of antibiotics to fight against the persistent evolution of pathogens that resist traditional antibiotic treatment. It has long been recognized that a delicate yet un-quantified balance between amphiphilicity and cationic charge is key to optimize the bactericidal efficiency and selectivity of these membrane-active antimicrobials (MAAs). The dilemma, however, is that the amphiphilic nature of MAAs that gives rise to their potency in disrupting microbial membranes is oftentimes also detrimental to human cells. Hydrophilic antimicrobial peptides and polymers generally have good biocompatibility, but they have received much less attention due to their low antimicrobial activity. In this work, we investigate whether polymer microstructure can be tuned to help hydrophilic polymers acquire high antimicrobial activity and selectivity. We evaluate and compare the different antimicrobial properties of linear and branched Poly(4-vinyl-N-methylpyridine iodide) (P4MVP) that are both hydrophilic and cationic. We show that P4MVP polymers can be designed as potent antimicrobial agents with negligible toxicity. We reveal a simple size-dependent antimicrobial activity and selectivity relationship that applies to both linear and branched P4MVP polymers. We also investigate the antimicrobial mechanism of P4MVP with different microstructures. We find that the antimicrobial potency of P4MVP is associated with their ability to remodel microbial membrane lipids by inducing a topological transition to form a two-dimensional inverted hexagonal structure, where P4MVP chains reside in the middle of the hexagonally packed lipid "pores". Collectively, our results show that it is possible to find another pathway to fight against the antibiotics-resistant pathogens by developing hydrophilic and cationic polymers that have both high antimicrobial activity and low toxicity.
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