A Type III Secretion Negative Clinical Strain of Pseudomonas aeruginosa Employs a Two-Partner Secreted Exolysin to Induce Hemorrhagic Pneumonia

Sylvie Elsen, Philippe Huber, Stéphanie Bouillot, Yohann Couté, Pierre Fournier, Yohann Dubois, Jean-François Timsit, Max Maurin, and Ina Attrée. Cell Host Microbe (2014) 15: 164-176

Speaker: Wei-Ting Li (李瑋庭)                                            Time: 15:10~16:00, Apr. 30, 2014

Commentator: Dr. Ching-Hao Teng (鄧景浩 老師)            Place: Room 601

Abstract:

Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium in most environments and an opportunistic human pathogen resistant to almost all available antibiotics. It causes a variety of diseases, including pneumonia, sepsis and infections of urinary tract, wounds and burns, in compromised individuals (1). Virulence of P. aeruginosa is typically attributed to its type III secretion system (T3SS) that injects T3SS effectors into host cells, and this is thought to play a key role in the pathogenesis of acute infections (2). In this work, the authors isolated a P. aeruginosa strain, named CLJ1, from a patient with hemorrhagic pneumonia. By comparing the nucleotide sequences of several genes, they found that CLJ1 is related to a non-virulent strain, PA7, and both strains lacked the T3SS locus and T3SS toxin genes. However, unlike PA7, CLJ1 was cytotoxic to the macrophage. In addition, CLJ1 was able to provoke mouse death and cross vascular barriers as efficiently as the T3SS-possessing strain, PAO1. Both the histological data and results of bronchoalveolar lavage fluid analysis showed that the mice infected by CLJ1 produced hemorrhagic pneumonia. The authors further found that although CLJ1 did not produce ExoU, the most potent cytotoxin (3), it could cause necrotic death of endothelial cells by damaging their cell membranes. By proteomic profile comparison, they identified Exolysin (ExlA), a hemolysin family pore-forming toxin, that was detected in the culture supernatant of CLJ1, but not PA7. Intriguingly, the exlBAoperon that encodes ExlA and an outer-membrane protein, ExlB, required for its export was also found in strain PA7. They then demonstrated that introduction of exlBA, but not exlA alone, in PAO1ΔpscD, which lacked exlBA and was deficient in T3SS, promoted endothelial cell membrane damage and induced lethal lung hemorrhage in mice. Altogether, the results strongly suggest thatExlA is the major virulence factor of the hypertoxic strain CLJ1.

References:

1.     Engel, J., and Balachandran, P. (2009). Role of Pseudomonas aeruginosa type III effectors in disease. Curr. Opin. Microbiol. 12, 61–66.

2.     Hauser, A.R. (2009). The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat. Rev. Microbiol. 7, 654–665.

3. Finck-Barbançon, V., Goranson, J., Zhu, L., Sawa, T., Wiener-Kronish, J.P., Fleiszig, S.M., Wu, C., Mende-Mueller, L., and Frank, D.W. (1997). ExoU expression by Pseudomonas aeruginosacorrelates with acute cytotoxicity and epithelial injury. Mol. Microbiol. 25, 547–557.