T3SS inhibitor

Project MBX

The type 3 secretion system (T3SS) is a virulence determinant found in Gram-negatives, such as P. aeruginosa.

During infection, this system secretes toxins that cause destruction of host tissues and dissemination of P. aeruginosa throughout the body. In collaboration with Microbiotix, the AMR Centre is developing a small-molecular T3SS inhibitor aimed at prevention and treatment of P. aeruginosa pneumonia.

The AMR Centre and Microbiotix entered into a co-development agreement to accelerate the development of Microbiotix’s lead bacterial virulence candidate on 14 September 2017. The two organisations will combine resources and their antimicrobial R&D expertise including the award of $3.2m, based on successful progression through milestones, from CARB-X in March 2017.

Target product

Prevention & Treatment of Ventilator-Associated Pneumonia caused by P. aeruginosa

  • Urgent unmet medical need
  • Common infection amongst critically ill patients
  • High mortality rates: >35% for MDR strains
  • Elevated health care costs: ~ $40,000 per episode
  • Novel anti-virulence approach

Mechanism

Inhibition of type III secretion system (T3SS)

  • Needle type projection delivers toxins into host cells
    • tissue destruction and inflammation
    • disruption of hosts immune response
  • T3SS inhibitors reverse this process:
    • prevent the establishment and dissemination of infections
    • avoid efflux and existing resistance mechanisms
U.S. Centers for Disease Control and Prevention - Medical Illustrator