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The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

Kantaraja Chindera1,2, Manohar Mahato3, Ashwani Kumar Sharma3

  • 1Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Royal College Street, London, NW1 0TU, UK.

Scientific Reports
|March 22, 2016
PubMed

Insights

Polyhexamethylene biguanide (PHMB) selectively kills bacteria by entering cells and condensing their chromosomes, not just disrupting membranes. This DNA-binding mechanism offers a new strategy against antimicrobial resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Understanding antimicrobial drug mechanisms is crucial for combating infections and resistance.
  • Polyhexamethylene biguanide (PHMB) is a widely used antimicrobial agent.
  • The established mechanism of PHMB involves bacterial membrane disruption.

Purpose of the Study:

  • To elucidate the selective mechanism by which PHMB kills bacteria over host cells.
  • To investigate an alternative antimicrobial mechanism for PHMB beyond membrane disruption.
  • To explore the potential of PHMB's DNA-binding properties in antimicrobial action.

Main Methods:

  • Observing bacterial cell entry and effects (division arrest, chromosome condensation) after PHMB treatment.
  • Analyzing PHMB interaction with isolated bacterial chromosomal DNA (nanoparticle formation).
  • Assessing PHMB's antimicrobial effects in combination with a DNA-binding ligand (Hoechst 33258).
  • Comparing PHMB entry and localization in bacterial versus mammalian cells.

Main Results:

  • PHMB entered various bacterial species, causing cell division arrest and chromosome condensation, suggesting DNA binding.
  • PHMB formed nanoparticles with bacterial DNA, and its growth inhibition was reduced by Hoechst 33258.
  • PHMB entered mammalian cells but was endosomally trapped, excluding it from nuclei.
  • PHMB demonstrated differential access to bacterial versus mammalian cellular DNA.

Conclusions:

  • PHMB selectively targets and condenses bacterial chromosomes, presenting a novel antimicrobial mechanism.
  • This DNA-level interaction provides a mechanism for selective bacterial killing over host cells.
  • The selective chromosome condensation mechanism may offer a way to overcome antimicrobial resistance, as resistance to PHMB has not been reported.

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