Pseudomonas aeruginosa Pore-Forming Exolysin and Type IV Pili Cooperate to Induce Host Cell Lysis

Pauline Basso, Michel Ragno, Sylvie Elsen, Emeline Reboud, Guillaume Golovkine, Stephanie Bouillot, Philippe Huber, Stephen Lory, Eric Faudry, Ina Attree

mBio vol. 8 no. 1 e02250-16

Speaker: Ke-Ying Hsieh (謝可盈)                                Time: 14:00~15:00, Oct, 11th, 2017

Commentator: Dr. Jenn-Wei Chen (陳振暐老師)     Place: Room 601

Abstract:

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe symptoms in the immunocompromised patients. Various Pseudomonas strains differ in the ability to induce host cell lysis and can be divided into two clades. One is PAO1/PA14 group which contain the well-studied type ІІІ secretion system and the other is PA7 group which lack the type ІІІ secretion system. Clinical isolates with type ІІІ secretion system genes tend to be more virulent. However, in the author’s previous studies ^[1], they’ve found a clinical isolate CLJ1 which is also a type ІІІ secretion negative strain (PA7-like) secret a toxin ExlA that causes hemorrhagic pneumonia. ExlA shows several sequence features found in two-partner secretion (TPS) system ^[2]. In this work, the authors try to characterize ExlA secretion and its biological function. First, they find ExlA and ExlB form a TPS system of P. aeruginosa and the C-terminal of ExlA is important for its cytotoxicity. Next, in their previous studies, it is show that the strain CLJ1 can induce plasma membrane rupture of epithelial cells. Hence they use red blood cells to confirm whether ExlA is a pore-forming toxin. Their results show that ExlA is indeed a pore-forming toxin and the diameter of the pore is 1.6 nm. But they also find the ExlA lacking the C-terminal region can still cause a mild hemolysis, suggesting that there may be other membrane-disruptive activity. Therefore, they use three recombinant proteins that represent different part of ExlA to perform liposome leakage assay and find that the C-terminal of ExlA can induce liposome leakage at low pH. They speculate that it may require conformational change of the C-terminal of ExlA to induce liposome leakage. Finally, they find the recombinant proteins cannot induce epithelial cell lysis, suggesting that other factor is involved in ExlA-mediated toxicity. From the transposon library, they find type IV pili mutant loss ExlA-mediated toxicity and only the complementation strain can restore its cytotoxicity. In conclusion, the authors demonstrate a novel example of pore-forming toxin of the TPS system cooperate with an adhesive appendage to induce host cell lysis.

References:

1.      Elsen S et al. 2014 A type III secretion negative clinical strain of Pseudomonas aeruginosa employs a two-partner secreted exolysin to induce hemorrhagic pneumonia. Cell Host Microbe 15:164 –176.

2.      Jacob-Dubuisson F et al. 2013 Two-partner secretion: as simple as it sounds? Res Microbiol 164:583–595.