Pseudomonas aeruginosa exoprotein A (rEPA), tetanus toxoid
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Pseudomonas aeruginosa exoprotein A (rEPA)
Pseudomonas aeruginosa is an opportunistic pathogen and a leading cause of hospital-acquired pneumonia. A 73kDa protein, designated Pseudomonas exoprotein A (PepA) is secreted by P. aeruginosa strain PA103. PepA is necessary for in vitro killing of epithelial cells as well as virulence in a mouse model of acute pneumonia. Several properties of PepA suggests that it is secreted by a type III system. Secretion occurrs without cleavage of a signal peptide and in low-calcium environments in the presence of a divalent cation chelator, as is the case for characterized P. aeruginosa type III secreted proteins. Secretion of PepA is absent from isogenic mutants with defective type III pathways. Finally, amino-terminal peptide sequence analysis indicates that the amino-terminal five residues of PepA are identical to those of ExoS and ExoT, two type III secreted proteins of P. aeruginosa. After secretion, PepA underwent cleavage at two sites, each with the sequence A-X-K-S, suggesting that the cleavage may be caused by a protease. A nucleotide sequence identical to the consensus element for binding of ExsA, a transcriptional activator of P. aeruginosa type III secretion genes, is located 84 bp 5' of the translational start codon. Analysis of transposon insertion mutants indicated that the carboxy terminus was required for cytotoxicity. Examination of respiratory clinical isolates demonstrated that pepA was a variable trait and probably acquired by horizontal transmission. Consistent with this hypothesis was the identification of a putative insertion element 94 bp 5' of the PepA translational start site. Analysis of G + C content of the PepA coding sequence and the adjacent insertion element suggested that they were acquired together from a different species. In summary, PepA is a secreted protein of P. aeruginosa that is necessary for epithelial cell cytotoxicity in vitro and virulence in a mouse model of pneumonia.