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No virulence without cooperation



After the discovery of a new bacterial virulence mechanism in Pseudomonas aeruginosa using a toxin called Exolysin, researchers from the Cancer Biology and Infection laboratory show that type IV pili are necessary for ExlA to exert its cytotoxic activity by creating a close contact between the bacterium and the host cell.

Published on 7 April 2017
Pseudomonas aeruginosa is the major opportunistic pathogen for humans. This antibiotic-resistant bacterium is responsible for serious infections in hospitals. The major virulence of P. aeruginosa is generally attributed to the type III secretion system (T3SS), which is a complex molecular machinery mimicking a needle injecting toxins directly into the host cell cytoplasm. Is this system universal in Pseudomonas aeruginosa or has this pathogen developed other strategies of virulence?

Recently, the Bacterial Pathogenesis and Cellular Responses team [Cancer Biology and Infection laboratory] has discovered a novel mechanism of virulence in clinical strains lacking SST3 and causing hemorrhagic pneumonias [1, 2]. This work deciphered the role of a new pore-forming toxin, called Exolysin (ExlA) in virulence. ExlA is characterized by the presence of several domains allowing its export through the bacterial membrane, its adhesion to cells and the formation of pores per se in the membrane of the target eukaryotic cell. Studies of ExlA and ExlA-induced cytotoxicity suggested that other bacterial factors might be necessary for the action of ExlA.
It is in search of such factors that Pauline Basso, a PhD student in the Bacterial Pathogenesis and Cellular Responses team, in collaboration with Prof. Lory's laboratory at Harvard Medical School in Boston, constructed a library of 7,000 mutants by transposition in an ExlA-positive clinical isolate. This library was then screened by high throughput imaging in search of mutants that became unable of inducing cytotoxicity [3]. By this approach, researchers have shown that extracellular appendages called type 4 pili (T4P) are necessary for the cytotoxicity and mobility of bacteria and their adhesion to eukaryotic cells. T4P allow close contact between the bacterium and the host cell, thus creating high local concentrations of ExlA, which then promotes the efficient formation of the membrane pore (
Figure).
This study proposes a cooperative model between two virulence systems in P. aeruginosa.


Cooperation between ExlA and type 4 pili (T4P). ExlB: protein in the outer membrane allowing the export of ExlA

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