• 1 Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Royal College Street, London, NW1 0TU, UK
  • 2 Nucleic Acids Research Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110 007, India
  • 3 Centre for Clinical Science &Technology, University College London, Wolfson House, 2-10 Stephenson Way, London NW1 2HE, UK
  • 4 Tecrea Ltd, London Bioscience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK
  • 5 Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243 122, India
  • 6 School of Biology, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK
  • 7 Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3C, 2200 Copenhagen N, Denmark
Sci Rep, 2016;6:23121.
PMID: 26996206 DOI: 10.1038/srep23121


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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.