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When the tenants turn toxic!



​Researchers at the Laboratory on Cancer Biology and Infection show how ExlA, a new toxin found in a strain of P. aeruginosa, causes necrosis of epithelial and endothelial cells in the lungs of infected mice and causes hemorrhagic pneumonias and allows dissemination of the bacteria in the body.

Published on 5 September 2017
The so-called "opportunistic" bacteria become pathogenic only when the body's defenses are weakened. In a healthy individual, they are either tolerated or eliminated. However, some opportunistic bacteria may acquire virulence factors that increase their pathogenicity. This is notably the case of recently isolated strains of the bacterium Pseudomonas aeruginosa which have been equipped with a formidable weapon, the pore-forming toxin ExlA.

P. aeruginosa can cause acute or chronic infections in certain situations: after physical, chemical or biological aggression, or in patients with chronic lung diseases or immunosuppressive therapy. The penetration of bacteria into the body takes place by transmigration through simple epithelia, as in pulmonary alveoli or the urinary system. However, several protection systems* exist and fiercely prevent access of bacteria to the internal mucosa. The second line of defense is the establishment of an inflammatory response, convening at the places of infection, the cells of innate immunity able to phagocyte and destroy the bacteria threatening the integrity of the mucosa.
Researchers from the Bacterial Pathogenesis and Cellular Responses team [Cancer Biology and Infection laboratory] have identified strains of P. aeruginosa with a new toxin: ExlA that forms pores in the plasma membrane. They show in this new study that this bacterial weapon causes the necrosis of epithelial and endothelial cells in the lungs of infected mice. This toxin causes haemorrhagic pneumonia and allows bacterial dissemination in the body (
Figure). The ExlA secreting strain can proliferate in the lungs because it does not induce the production of pro-inflammatory cytokines and does not trigger an immune response sufficient to be destroyed. On the other hand, when the blood system of mice is infected, the bacterium is rapidly destroyed because it is in the direct presence of neutrophils and the complement system.

* for example mucociliary clearance, surfactant, defensins, resident macrophages ...
This work was done in collaboration with Benoît Gallet and Guy Schoehn of the IBS for electron microscopy of tissues, and with the team of Emmanuel Lémichez in Nice for the bacteremic model.



The secretion of the ExlA toxin by bacteria causes necrosis of epithelial and endothelial cells, which causes the rupture of the alveolar-capillary barrier and allows bacterial dissemination in the body.

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