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Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague

Yaron Vagima1, David Gur1, Moshe Aftalion1

  • 1Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel.

Viruses
|April 23, 2022
PubMed

Insights

Bacteriophage therapy shows promise for treating plague caused by multidrug-resistant Yersinia pestis. Combining phage therapy with antibiotics offers a synergistic protective effect, crucial for emergency plague outbreaks.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Bacteriophage Therapy

Background:

  • Plague, caused by Yersinia pestis, has historically caused devastating pandemics.
  • Antibiotics are effective for plague, but multidrug-resistant strains necessitate alternative treatments.
  • Bacteriophage therapy has demonstrated efficacy against multidrug-resistant pathogens.

Purpose of the Study:

  • To evaluate the efficacy of bacteriophage therapy against pneumonic plague in a mouse model.
  • To assess the combination of phage therapy with antibiotics for treating multidrug-resistant Yersinia pestis infections.

Main Methods:

  • Utilized a mouse model of pneumonic plague.
  • Administered bacteriophages фA1122 and PST, alone and in combination with ceftriaxone.
  • Assessed mortality, bacterial proliferation in lungs, and bacteremia.
  • Performed in vitro phage proliferation assays in blood.

Main Results:

  • Phage therapy alone delayed mortality and reduced lung bacterial load but did not prevent bacteremia.
  • In vitro studies indicated that blood inhibits phage lytic activity.
  • Combination therapy of phages and ceftriaxone resulted in 100% survival.

Conclusions:

  • Phage therapy alone has limitations in treating plague due to inhibitory effects of blood.
  • Combination therapy with phages and ceftriaxone demonstrates a synergistic protective effect.
  • This combinatorial approach offers a potential strategy for managing multidrug-resistant Yersinia pestis during plague outbreaks.
Keywords:
PSTYersinia pestisantibiotic resistanceantibiotic therapyceftriaxonephage therapyphage–antibiotic combinationplagueфA1122

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