Novel method to control pathogenic bacteria on human mucous membranes.
Nearly all infections begin at a mucous membrane site. Also, the human mucous membranes are a reservoir for many pathogenic bacteria found in the environment (that is, pneumococci, staphylococci, streptococci), some of which are resistant to antibiotics. Clearly, if this human reservoir can be reduced or eliminated, the incidence of disease will be markedly reduced. However, compounds designed to eliminate this reservoir are not available. Towards this goal, we have exploited the highly lethal effects of bacteriophage lytic enzymes (lysins) to specifically destroy disease bacteria on mucous membranes. Such lysins are used by the phage to release their progeny at the end of their replicative cycle. We have identified and purified these enzymes and found that when applied externally to gram-positive bacteria, they are killed seconds after contact. For example, 10(7) S. pyogenes are reduced to undetectable levels 10 s after enzyme addition. A feature of these enzymes is their high specificity; that is, streptococcal lysins kill streptococci and pneumococcal lysins kill pneumococci without effects on the normal flora organisms. In vivo, an oral colonization model for S. pyogenes and a nasal colonization model for S. pneumoniae were developed to test the capacity of the lysins to kill organisms on these surfaces. In both cases, when the animals were pre-colonized with their respective bacteria then treated with a small amount of lysin, specific for the colonizing organism, all the animals were found to be free of colonizing bacteria shortly after lysin treatment. Thus, lysins may be added to our armamentarium to control antibiotic-resistant bacteria.
Fischetti
Vincent A
VA
The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA. vaf@mail.rockefeller.edu
D001419:Bacteria / Q000472:pathogenicity*; D001694:Biological Warfare; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal; D009092:Mucous Membrane / Q000276:immunology / Q000382:microbiology*
D004798:Enzymes