1. The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes.
- Author
-
Chindera K, Mahato M, Sharma AK, Horsley H, Kloc-Muniak K, Kamaruzzaman NF, Kumar S, McFarlane A, Stach J, Bentin T, and Good L
- Subjects
- Animals, Anti-Bacterial Agents metabolism, Bacillus megaterium drug effects, Bacillus megaterium genetics, Bacillus megaterium metabolism, Biguanides metabolism, CHO Cells, Cattle, Cell Membrane Permeability drug effects, Chromosome Structures drug effects, Cricetinae, Cricetulus, Escherichia coli drug effects, Escherichia coli genetics, Escherichia coli metabolism, HEK293 Cells, HeLa Cells, Horses, Humans, Mice, Microbial Sensitivity Tests, Mycobacterium smegmatis drug effects, Mycobacterium smegmatis genetics, Mycobacterium smegmatis metabolism, Salmonella typhimurium drug effects, Salmonella typhimurium genetics, Salmonella typhimurium metabolism, Stress, Physiological drug effects, Anti-Bacterial Agents pharmacology, Biguanides pharmacology, Chromosomes, Bacterial genetics
- Abstract
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.
- Published
- 2016
- Full Text
- View/download PDF