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A8

Ph Huber, BIG,

A novel pore-forming toxin from Pseudomonas aeruginosa: mode of action and structure

 Background:

Pseudomonas aeruginosa is a leading agent of nosocomial infections. The most aggressive strains possess a secretion system injecting various toxins directly in the cytoplasm of target cells. We have recently isolated a novel hyper-toxic clinical strain of P. aeruginosa, named CLJ1 that does not possess this secretion system, but instead releases a pore-forming toxin called ExlA. In addition to membrane toxicity, CLJ1 demonstrates high proteolytic activities towards E-cadherin, an intercellular junction adhesive protein required for epithelium integrity. Infection of mouse lungs with CLJ1 induced an hemorrhagic pneumonia, a symptom that was also observed in the patient from whom the strain originates.

Objectives:

Team:

Philippe Huber, Research director CEA

Ina Attrée, Research director CNRS and group leader

Sylvie Elsen, Staff researcher CNRS

Stéphanie Bouillot, Technician CEA

Andrea Dessen, Research director and group leader

Viviana Job, staff researcher

Guy Schoehn, Research director and group leader

Benoît Gallet, Staff scientist

Emeline Reboud, PhD student from october 2014

Achievements :

  1. Eighteen other ExlA strains have been collected from 5 continents, demonstrating that these taxonomic outliers have already spread worldwide. The genetic analyses show that the strains belong to two phylogenetically divergent groups, probably originating from two different ancestors. Their cytotoxicity is highly variable and is correlated with ExlA secretion levels. The highly virulent ExlA strains are toxic for most cell types. Furthermore, the strains exhibited differential toxicity in mouse and in planta, suggesting that animals and plants are sensitive to different modes of virulence.

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