Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic

Divakara S S M Uppu1, Sandip Samaddar1, Chandradhish Ghosh1

  • 1Chemical Biology & Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur, Bangalore 560064, India.

Biomaterials
|October 11, 2015
PubMed

Insights

Novel cationic polymers effectively disrupt drug-resistant bacterial biofilms, including Acinetobacter baumannii, and reduce infection burden in mice. These polymers show broad-spectrum efficacy with low toxicity and prevent resistance development, offering potential for medical device disinfection and infection treatment.

Area of Science:

  • Polymer chemistry
  • Microbiology
  • Infectious diseases

Background:

  • Bacterial biofilms are a primary cause of persistent human infections.
  • Gram-negative bacteria like Acinetobacter baumannii are challenging to treat due to antibiotic resistance and biofilm formation.
  • A. baumannii persists in healthcare settings by forming biofilms on surfaces.

Purpose of the Study:

  • To develop novel cationic polymers capable of disrupting established multi-drug resistant A. baumannii biofilms.
  • To evaluate the efficacy of these polymers in reducing bacterial burden in a mouse infection model.
  • To assess the polymers' antibacterial spectrum, toxicity, and potential for resistance development.

Main Methods:

  • Synthesis of maleic anhydride-based cationic polymers with amide side chains.
  • Testing biofilm disruption and antibacterial activity against A. baumannii, MRSA, VRE, and clinical isolates.
  • Evaluating polymer toxicity in mammalian cells.
  • Assessing bacterial resistance development to the polymers in vitro.
  • Investigating the mechanism of action, including bacterial membrane interaction.

Main Results:

  • Polymers significantly disrupted multi-drug resistant A. baumannii biofilms.
  • A significant reduction in bacterial burden was observed in mice with chronic A. baumannii burn wound infections (p < 0.0001).
  • Polymers demonstrated potent antibacterial activity against MRSA, VRE, and MDR A. baumannii with minimal mammalian cell toxicity.
  • Selective toxicity was linked to polymer hydrophobicity.
  • Mechanism involves bacterial membrane depolarization, permeabilization, and energy depletion.
  • No detectable resistance developed against the polymers after multiple passages, unlike rapid resistance to conventional antibiotics.

Conclusions:

  • Novel cationic polymers effectively target and disrupt established bacterial biofilms, including those formed by antibiotic-resistant pathogens.
  • These polymers show promise for treating chronic wound infections and disinfecting medical devices.
  • The polymers offer a new therapeutic strategy with a low risk of resistance development.

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