Rahme Lab
Multi-Host Pathogenesis
and Anti-infective agents

 
   
 

 

 

 

 

 

 

 

Click to see overview figure

Click to see the Mutants Table

 


Overview

image Each partner in a host-pathogen antagonistic interaction employs specialized strategies, the host to respond to and combat the pathogen, and the pathogen to circumvent these host defenses. Indeed, the ultimate success of an infectious agent is often determined by the interplay between these competing strategies at the early stages of infection. Host defenses can be general and directed against many pathogens, or conversely, dedicated to individual threats; while pathogen mechanisms can exploit normal host processes by interfering with their regulation or activity.

The Rahme Laboratory focuses on the development of improved clinical treatments to prevent, halt or limit bacterial infections at an early stage, specifically those caused by the human opportunistic bacterium Pseudomonas aeruginosa. Research into the P. aeruginosa host-pathogen interaction has both basic and practical importance: this bacterium infects a remarkably broad array of species, including plants, insects, and vertebrates; and it is a major agent of grave drug-resistant infections in trauma, cystic fibrosis, and immunocompromised patients, including those suffering of, severe burn injuries, or cancer patients undergoing radiation therapy or chemotherapy.

Our research has two ultimate goals: (1) to elucidate mechanisms of bacterial pathogenesis, and (2) to identify host defense pathways. Thus, we seek to identify pathogen and host mechanisms that respectively mediate or restrict P. aeruginosa pathogenesis, and ultimately to develop host-protective interventions that manipulate the identified pathways.

We have pioneered the use of non-vertebrate hosts to study human microbial pathogenesis and demonstrated that the opportunistic bacterium P. aeruginosa can cause disease in both plants and animals using a shared subset of virulence factors. The identification of conserved mechanisms of pathogenesis enabled systematic high-throughput identification of critical pathogenicity factors and indicated that therapeutics for treating infections can be developed in genetically tractable model hosts. We use plants, yeast and insects, as adjunct to mice, to investigate the genetic and molecular bases of P. aeruginosa virulence. This non-vertebrate host approach allows human pathogenesis to be modeled in experimentally amenable organisms in a high-throughput manner. Our ability to genetically manipulate both pathogen and host permits concentrated examination of virulence-defense interactions.