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The Fischetti lab is working to understand the earliest events that occur when gram-positive bacteria interact with human tissues and cause disease. As new antibiotics are proving futile against resistant strains of bacteria, the Fischetti lab has developed a method using phage lysins to identify weak points in bacterial cells that can be exploited for antibiotic development. Because bacteria use their surface molecules to attack and invade human tissues, a better understanding of how they anchor these molecules in their cell walls could lead to strategies to prevent infection.
His research is aimed at developing strategies to interfere with these events, such as vaccines to induce a mucosal immune response and enzymes derived from bacteria-killing viruses known as phage to prevent and treat infections. Fischetti works with both gram-positive and gram-negative bacteria, such as streptococci, staphylococci, anthrax, and acinetobacter to develop unique treatment strategies to prevent infection.
Fischetti’s studies have shown that when small amounts of phage lysins are administered to infected mice, disease-causing bacteria are rapidly destroyed.

Fischetti’s lab developed a method of drilling through the thick cell walls of gram-positive bacteria while keeping them intact. Using this approach, the Fischetti lab has identified a novel target, the enzyme 2-epimerase, involved in cell wall biosynthesis and critical for bacterial survival.
The M surface protein is the major virulence factor of group A streptococci because of its ability to impede human white blood cells.
His approach involves novel anti-infectives and the use of phage lytic enzymes to both prevent infection and remove pathogenic bacteria from infected tissues. The enzymes are extremely potent; micrograms can destroy millions of organisms within seconds. The technique enabled the Fischetti lab to access the bacterial cytoplasm with labeled antibodies to study intracellular molecules that were previously inaccessible. A novel inhibitor based on this target, Epimerox, was found to protect animals from lethal infection, and no bacterial resistance has been found to Epimerox.
Beyond the chromosome: the prevalence of unique extra-chromosomal bacteriophages with integrated virulence genes in pathogenic Staphylococcus aureus.
Novel bacteriophage lysin with broad lytic activity protects against mixed infection by Streptococcus pyogenes and methicillin-resistant Staphylococcus aureus.

Cellular aspects of the distinct M protein and SfbI anchoring pathways in Streptococcus pyogenes. Synergism between a novel chimeric lysin and oxacillin protects against infection by methicillin-resistant Staphylococcus aureus. They are also highly specific and, unlike antibiotics, only kill the disease-causing bacteria, without harming the beneficial bacteria. Fischetti and his collaborators have shown that systemic administration of the phage enzyme Cpl-1 can rescue infected mice and completely reverse lung tissue damage if given within 24 hours postinfection. Fischetti’s lab shows the region used to attach the M protein to the streptococcal cell surface is highly conserved in all gram-positive bacteria, indicating that the mechanism for anchoring surface proteins in bacteria is also conserved. Since bacteria cannot cause infection without surface proteins, a molecule that blocks surface protein attachment would be broadly applicable to different gram-positive bacteria.

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Comments to “Do digestive enzymes interfere with vitamins”

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