Type III Secretion System (T3SS)

 

Ventilator-associated-pneumonia/CF/bacteremia

Pseudomonas aeruginosa virulence target
Lead Optimization

  • Microbiotix’s unique approach to targeting drug-resistant Gram-negative
    bacteria focuses on bacterial virulence, specifically the type III secretion
    system of Pseudomonas aeruginosa. The novel inhibitors, discovered by
    Microbiotix scientists, have been shown to reverse the pathogen’s disruption
    of the host innate immune response to infection and are not subject to
    efflux or existing antibiotic resistance mechanisms.
  • During infection, this system secretes toxins that cause destruction
    primarily of neutrophils and macrophages, disrupting the host’s immune
    response, thus promoting the establishment and dissemination of infections.

Mechanism: Inhibition of type III secretion system (T3SS)

  • Needle type projection (PscF) delivers toxins into host cells,
    destroying macrophages and neutrophils, thus disrupting the host’s immune response
  • T3SS inhibitors, targeting PscF, reverse this process, preventing
    the establishment and dissemination of infection, while avoiding
    efflux and existing resistance mechanisms

 

Prevention and treatment of ventilator-associated pneumonia (VAP) caused by P. aeruginosa

  • VAP is an urgent medical need.
  • Common infection in critically ill patients.
  • High mortality rates: >35% for MDR strains.
  • Elevated healthcare costs: ~ $40,000 per episode.
  • Novel anti-virulence approach.

Strong partnerships

  • Microbiotix was among the first recipients of funding ($3.2 million) from
    CARB-X (Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator).
  • Microbiotix and its development partner, the UK’s AMR Centre, have
    combined resources and antimicrobial R&D expertise to accelerate the
    development of Microbiotix’s lead bacterial anti-virulence candidate.

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