抗菌剂
DNA
细菌
细菌圆形染色体
微生物学
细胞分裂
生物
作用机理
细胞生物学
细菌遗传学
细菌细胞结构
细胞
化学
生物物理学
生物化学
遗传学
大肠杆菌
DNA复制
基因
体外
作者
Kantaraja Chindera,Manohar Mahato,Ashwani Sharma,Harry Horsley,Klaudia Kloc-Muniak,Nor Fadhilah Kamaruzzaman,Satish Kumar,Alexander McFarlane,James E. M. Stach,Thomas Bentin,Liam Good
摘要
To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance.
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