Antibody-based bacterial cytotoxicity mediated by mechanisms independent of CDC and ADCC

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In addition to their well-characterized functions of antigen recognition for destruction of specific targets through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), numerous antibodies, termed Abzymes, have been found to possess catalytic abilities such as hydrolysis of nucleotides, proteins, and polysaccharides, phosphorylation of proteins and lipids, and generation of free radicals. We have found that a monoclonal antibody (mAb), namely anti-Pseudomonas aeruginosa O6ad lipopolysaccaride (LPS) IgG1, and its recombinant antibody (rAb) fragments (Fab and scFv) exhibit cytotoxic activities against their specific target bacterium independent of ADCC and CDC. Our preliminary unpublished data indicate that this mAb has co-evolved two functions onto one molecule: specific binding to the surface of a pathogen, and the ability to kill it per se. We propose a five-year research program to test the hypothesis that this mAb and its fragments are catalytic in nature, and to elucidate the specific killing mechanism through experimentation involving biochemical, molecular, physiological, structural, analytic, immunological, genetic, and pharmacological techniques. We will also search for other antibodies with specific bactericidal characteristics, and to compare killing mechanisms for further understanding of this phenomenon. It is anticipated that research outcomes will result in greater understanding a novel mechanism of cytotoxicity with tremendous potential for further development of applications in medicine and health.