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Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport
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Bile Acid Oligomers and Their Combination with Antibiotics To Combat Bacterial Infections

Poonam Singla1, Priyanka Dalal2, Mahaldeep Kaur2

  • 1Department of Chemistry and Centre for Advanced Studies in Chemistry , Panjab University , Chandigarh 160014 , India.

Journal of Medicinal Chemistry
|November 3, 2018
PubMed

Insights

New bile acid oligomers show potent antibacterial activity against resistant bacteria like MRSA and VRE. These compounds also enhance existing antibiotics and inhibit biofilms without observed toxicity.

Area of Science:

  • Microbiology
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • Antimicrobial resistance, particularly from strains like methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA), poses a significant global health threat.
  • Developing novel antimicrobial agents with unique mechanisms of action is crucial to combat evolving bacterial resistance.
  • Membrane-targeting antibiotics are hypothesized to be less prone to resistance development.

Purpose of the Study:

  • To design and synthesize novel bile acid oligomers with specific topologies.
  • To evaluate the antibacterial activity of these oligomers against Gram-positive bacteria, including resistant strains.
  • To assess the potential of these compounds to overcome antibiotic resistance and inhibit bacterial biofilms.

Main Methods:

  • Synthesis of bile acid oligomers with tailored linker structures.
  • In vitro testing of antibacterial efficacy against various bacterial strains, including antibiotic-resistant clinical isolates.
  • Combination studies with existing antibiotics to evaluate synergistic effects.
  • Biofilm inhibition assays.
  • Cell viability assays using HEK293 cells to assess cytotoxicity.

Main Results:

  • The synthesized bile acid oligomers demonstrated potent and selective antibacterial activity against Gram-positive bacteria.
  • Lead compounds effectively enhanced the efficacy of various known antibiotics when used in combination.
  • Active dimers showed effectiveness against antibiotic-resistant Staphylococcus aureus isolates, including multidrug-resistant strains.
  • Significant inhibition of Staphylococcus aureus biofilm formation was observed.
  • No adverse effects were detected in cell viability assays.

Conclusions:

  • Bile acid oligomers represent a promising class of novel antimicrobial agents.
  • These compounds exhibit potent activity against challenging bacterial pathogens and can resensitize bacteria to existing therapies.
  • The ability to inhibit biofilms and lack of observed toxicity highlight their therapeutic potential in combating antimicrobial resistance.

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