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Treatment of Gram-negative bacterial infections by potentiation of antibiotics

Thomas P Zabawa1, Michael J Pucci1, Thomas R Parr1

  • 1Spero Therapeutics, 675 Massachusetts Avenue, Cambridge, MA 02139, United States.

Current Opinion in Microbiology
|May 28, 2016
PubMed

Insights

New potentiator molecules are being developed to combat antibiotic-resistant Gram-negative bacterial infections. These compounds disrupt the bacterial outer membrane, enhancing antibiotic effectiveness and addressing critical treatment challenges.

Area of Science:

  • Antimicrobial resistance
  • Bacterial pathogenesis
  • Drug discovery

Background:

  • Antibiotic-resistant Gram-negative bacterial infections pose significant clinical challenges.
  • The outer membrane of Gram-negative bacteria acts as a barrier to many antibiotics.

Purpose of the Study:

  • To explore advanced potentiator molecules for combination therapy against resistant Gram-negative infections.
  • To overcome the permeability barrier of Gram-negative bacterial outer membranes.

Main Methods:

  • Evaluation of novel cationic potentiator molecules.
  • Investigating the mechanism of outer membrane disruption by potentiators.
  • Assessing potentiators for use in combination therapy.

Main Results:

  • Potentiator molecules disrupt the negatively charged outer membrane of Gram-negative bacteria.
  • This disruption allows otherwise impermeant molecules to enter bacterial cells.
  • Advanced potentiator molecules show promise in overcoming antibiotic resistance.

Conclusions:

  • Potentiator molecules offer a viable strategy to restore antibiotic susceptibility in resistant Gram-negative pathogens.
  • Development of advanced potentiators aims to mitigate toxicity issues associated with earlier compounds.
  • Combination therapy with potentiators represents a promising approach for treating challenging Gram-negative infections.

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