Department of Microbiology and Immunology, Emory University School of Medicine, Emory Antibiotic Resistance Center, Atlanta, Georgia 30322, United States.
Department of Chemistry and Department of Medicine, University of Wisconsin, Madison, Wisconsin 53706, United States.
ACS Infect Dis. 2021 May 14;7(5):1236-1247. doi: 10.1021/acsinfecdis.0c00843. Epub 2021 Mar 19.
A wide range of synthetic polymers have been explored for antimicrobial activity. These materials usually contain both cationic and hydrophobic subunits because these two characteristics are prominent among host-defense peptides. Here, we describe a series of nylon-3 polymers containing only cationic subunits and their evaluation against the gastrointestinal, spore-forming pathogen . Despite their highly hydrophilic nature, these homopolymers showed efficacy against both the vegetative and spore forms of the bacterium, including an impact on spore germination. The polymer designated P34 demonstrated the greatest efficacy against strains, along with low propensities to lyse human red blood cells or intestinal epithelial cells. To gain insight into the mechanism of P34 action, we evaluated several cell-surface mutant strains of to determine the impacts on growth, viability, and cell morphology. The results suggest that P34 interacts with the cell wall, resulting in severe cell bending and death in a concentration-dependent manner. The unexpected finding that nylon-3 polymers composed entirely of cationic subunits display significant activities toward should expand the range of other polymers considered for antibacterial applications.
人们探索了广泛的合成聚合物以获得抗菌活性。这些材料通常包含阳离子和疏水性亚基，因为这两个特征在宿主防御肽中很突出。在这里，我们描述了一系列仅包含阳离子亚基的尼龙-3 聚合物及其对胃肠道、孢子形成病原体的评估。尽管这些均聚物具有很强的亲水性，但它们对细菌的营养体和孢子形式都有效，包括对孢子萌发的影响。指定为 P34 的聚合物对 菌株表现出最大的功效，同时对裂解人红细胞或肠上皮细胞的倾向较低。为了深入了解 P34 作用的机制，我们评估了几种 表面突变菌株，以确定对生长、活力和细胞形态的影响。结果表明，P34 与细胞壁相互作用，导致细胞严重弯曲并以浓度依赖的方式死亡。出人意料的是，完全由阳离子亚基组成的尼龙-3 聚合物对 显示出显著的活性，这应该扩大了用于抗菌应用的其他聚合物的范围。
