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Phage therapy for extremely drug resistant Shigella

Westmead Institute for Medical Research

Grant:
  • Early-Mid Career Fellowship
Date Funded:
  • 17 May, 2021
Chief Investigator/s:
  • Professor Jon Iredell

Research intent

Development of phage combinations that kill the agent of bacterial dysentery (Shigella) ‘hiding’ inside cells and restore the power of antibiotics.

What is the issue?

Shigella, the most severe of the bacterial diarrhoeal pathogens and a leading cause of childhood mortality around the world, has become extremely resistant (XDR) to antibiotic. None of the antimicrobials we usually rely on remain effective. This is a growing epidemic in adults in NSW (in 2019, 59% Shigella cases reported were resistant to different classes of antibiotics. https://www.health.nsw.gov.au) and a great threat to children, especially in our Aboriginal and CALD communities (public health priorities-control guidelines, https://www.health.nsw.gov.au). New therapies are urgently needed as all our antibiotics are failing.

What does the research aim to do and how?

We will define the most potent combinations of bacteriophages, and in concert with antibiotics, to treat Shigella inside the mammalian cell, where it replicates. We will do this by both in vitro and ex vivo approach.

Phages will be extensively characterised (e.g., WGS, electron microscopy, stability assays). We will design companion diagnostic protocols to monitor bacterial and phage kinetics and host response. We will make these alternative treatments available for therapy where current antibiotics fail.