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Vince A. Fischetti, Ph.D.
Professor and Chair, Laboratory of Bacterial Pathogenesis,
Rockefeller University, New York
Dr. Fischetti has over 40 years experience in the anti-infectives field. He is Professor and Chair of the Laboratory of Bacterial Pathogenesis and Immunology at the Rockefeller University in New York. Dr. Fischetti is a fellow of the American Academy of Microbiology, and is the recipient of two NIH MERIT awards. He has been editor-in-chief of the scientific journal Infection and Immunity for 10 years, and serves as advisory editor for the Journal of Experimental Medicine and Trends in Microbiology.
Dr. Fischetti serves on the scientific advisory board and trustee of the Trudeau Institute. He has published approximately 150 primary research articles, and 70 textbook chapters as well as being an inventor of 40 issued patents.
Dr. Fischetti received a Ph.D. in Microbiology from New York University.
About the lecture
"Controlling Pathogenic Bacteria with Phage Lytic Enzymes"
Bacteriophage lytic enzymes are highly evolved molecules used by the phage to quickly destroy the bacterial cell wall to release phage progeny. We have exploited the rapid and lethal action of these enzymes to destroy pathogenic and biological warfare bacteria on mucous membranes and in blood. These enzymes in general are specific for the species or strain from which they were produced, thus avoiding destruction of the surrounding normal commensal organisms found on mucosal surfaces.
We now have enzymes that are specific for S. pyogenes, S. pneumoniae, B. anthracis, S. aureus, E. faecalis/E. faecium and group B streptococci. Our results show that in vitro 107 bacteria can be reduced to sterility seconds after enzyme contact. In animal model experiments, we were able to colonize mice with either streptococcal or pneumococcal species (orally or nasally) and remove them completely with phage enzymes delivered to these sites using a single enzyme dose.
In a septicemia model with S. pneumoniae, bacteria are reduced by >2-logs from the blood of infected animals with a single intravenous dose of enzyme. A lytic enzyme called PlyG from the gamma-phage of B. anthracis was specific for all worldwide isolates of B. anthracis. The enzyme specifically killed B. anthracis with no effect on other bacilli or other organisms. When >1 LD100 of B. anthracis bacilli were delivered i.v. to mice we observed a progression of symptoms, leading to survival of only 10% of animals followed for 12 days. When PlyG was injected i.v. 15 min after infection, a significant therapeutic effect was observed in which 90% of the mice recovered fully. Resistance to the enzymes has not been found nor do antibodies neutralize their activity.
Furthermore, a combination of antibiotic and enzyme has been shown to work synergistically resulting in efficient lethal activity in cases of antibiotic resistant bacteria. Thus, phage lytic enzymes are a new reagent that may be used in hospitals, nursing homes and the general population to control antibiotic resistant pathogenic bacteria in blood and on mucosal surfaces, offering a capability previously unavailable.
Quoted from the 2006-2007 Loyd E. Harris Lecture Series Announcement Brochure