PROTECTION AGAINST EXOTOXIN-A (ETA) AND PSEUDOMONAS-AERUGINOSA INFECTION IN MICE WITH ETA-SPECIFIC ANTIPEPTIDE ANTIBODIES

Pseudomonas aeruginosa is an opportunistic pathogen that causes seriou s and sometimes fatal infections in the compromised host, especially i n patients,vith major trauma or thermal injuries. Exotoxin A (ETA) is the major and most lethal virulence factor produced by this ubiquitous microorganism. In a recent study (H. S. Elzaim, A. K. Chopra, J. W. P eterson, R. Goodheart, and J. P. Heggers, Infect. Immun. 66:2170-2179, 1998), we identified two major epitopes, one within the translocation domain (amino acid [aa] residues 289 to 333) of ETA and another withi n the enzymatic domain (aa 610 to 638), by using a panel of antipeptid e antibodies. Synthetic peptides representing these two epitopes induc ed ETA-specific antibodies which were able to abrogate the cytotoxic a ctivity of ETA, as measured by incorporation of [H-3]leucine into 3T3 fibroblasts. In the present study, these antibodies were tested for th e ability to provide protection against ETA and infection with a toxin -producing strain of P. aeruginosa in a mouse model. Antibodies to eit her of the synthetic peptides conferred protection against ETA. Also, when used for immunization, both peptides induced active immunity to E TA in mice. Antibodies to the peptide representing a region within the enzymatic domain of ETA, in combination with the antibiotic amikacin, enhanced the survival of mice infected with a toxin-producing strain of P. aeruginosa. Thus, antipeptide antibodies specific for ETA might be paired with antibiotic treatment for passive immunization of patien ts suffering from P. aeruginosa infection.