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Scientific reports2016; 6; 23121; doi: 10.1038/srep23121

The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes.

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.
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Publication Date: 2016-03-21 PubMed ID: 26996206PubMed Central: PMC4800398DOI: 10.1038/srep23121Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the method by which the antimicrobial polymer PHMB kills bacteria by selectively binding and condensing bacterial chromosomes without disrupting the cells’ membrane, contrasting with the previously accepted model.

Introduction and Objective:

  • The purpose of this study is to examine how the antimicrobial polymer Polyhexamethylene Biguanide (PHMB) effectively destroys bacteria, crucial in counteracting potential infections and antibiotic resistance.

Accepted Model and New Findings:

  • The previously accepted model of PHMB’s function assumes its disruption of the bacterial cell membrane.
  • However, the study observed an alternative mechanism where PHMB enters various bacterial cells, arrests cell division, and causes chromosome condensation, suggesting possible DNA binding.

Verification of Alternative Mechanism:

  • PHMB’s DNA-level mechanism was further confirmed by noting the formation of nanoparticles upon mixing PHMB with isolated bacterial chromosomal DNA.
  • The combination of PHMB with a DNA binding ligand (Hoechst 33258) suppressed its growth effect, reinforcing the DNA binding hypothesis.

PHMB Action on Mammalian Cells:

  • The research also noted that while PHMB is capable of entering mammalian cells, it is trapped within endosomes and excluded from the cell nuclei.
  • This showcases differential access between bacterial and mammalian cellular DNA, highlighting PHMB’s selective binding and condensation of bacterial chromosomes.

Implication on Antimicrobial Resistance:

  • Since there have been no reported cases of resistance to PHMB, the study concludes that selective chromosome condensation provides a new perspective for antimicrobial action that may not succumb to resistance, thereby indicating a potentially effective and lasting treatment against harmful bacteria.

Cite This Article

APA
Chindera K, Mahato M, Sharma AK, Horsley H, Kloc-Muniak K, Kamaruzzaman NF, Kumar S, McFarlane A, Stach J, Bentin T, Good L. (2016). The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes. Sci Rep, 6, 23121. https://doi.org/10.1038/srep23121

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 6
Pages: 23121
PII: 23121

Researcher Affiliations

Chindera, Kantaraja
  • Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Royal College Street, London, NW1 0TU, UK.
  • Tecrea Ltd, London Bioscience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK.
Mahato, Manohar
  • Nucleic Acids Research Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110 007, India.
Sharma, Ashwani Kumar
  • Nucleic Acids Research Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110 007, India.
Horsley, Harry
  • Centre for Clinical Science &Technology, University College London, Wolfson House, 2-10 Stephenson Way, London NW1 2HE, UK.
Kloc-Muniak, Klaudia
  • Tecrea Ltd, London Bioscience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK.
Kamaruzzaman, Nor Fadhilah
  • Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Royal College Street, London, NW1 0TU, UK.
  • Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, Locked bag 36, Pengkalan Chepa, 16100 Kota Bharu, Kelantan, Malaysia.
Kumar, Satish
  • Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243 122, India.
McFarlane, Alexander
  • School of Biology, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK.
Stach, Jem
  • School of Biology, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK.
Bentin, Thomas
  • Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3C, 2200 Copenhagen N, Denmark.
Good, Liam
  • Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Royal College Street, London, NW1 0TU, UK.
  • Tecrea Ltd, London Bioscience Innovation Centre, 2 Royal College Street, London, NW1 0NH, UK.

MeSH Terms

  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacillus megaterium / drug effects
  • Bacillus megaterium / genetics
  • Bacillus megaterium / metabolism
  • Biguanides / metabolism
  • Biguanides / pharmacology
  • CHO Cells
  • Cattle
  • Cell Membrane Permeability / drug effects
  • Chromosome Structures / drug effects
  • Chromosomes, Bacterial / genetics
  • 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

Conflict of Interest Statement

The authors declare competing interests. KC and LG are inventors on a filed patent application WO2013054123.

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Citations

This article has been cited 82 times.
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