Phage Therapy of Glanders
Use of Bacteriophages and Phage Lytic Enzymes as a Novel Treatment for Glanders
Tech Area / Field
- MED-DRG/Drug Discovery/Medicine
3 Approved without Funding
State Research Center for Applied Microbiology and Biotechnology, Russia, Moscow reg., Obolensk
Project summaryHistorically, resistance to a new antibiotic has been observed within the natural bacterial population after a few years of its first widespread commercial use. Selective pressures resulting from the continued use of that and antibiotics with related activities has allowed the proliferation of antibiotic resistance - often carried on mobile genetic elements including conjugal plasmids and transposons, among all bacterial genera. Naturally occurring pathogenic bacteria are known that are resistant to therapeutic levels of all known antibiotics. It is trivial to isolate antibiotic mutants of almost any bacterium in the laboratory and it is almost certain that any intentional use of bacteria as biowarfare agents will involve antibiotic resistant strains. It is also likely that the use of bacterial biowarfare agents will involve specific strains that are insensitive to neutralization by antisera effective for natural strains. In this context, a fundamentally different approach to preventing, controlling, or curing disease caused by pathogenic bacteria would provide an invaluable addition to standard therapeutic procedures.
In the past few years, the western world has begun to re-evaluate the use of lytic bacteriophages as a therapeutic agent. Bacteriophages were once promoted commercially as antibacterials by the west, but their use fell into disfavor partly because of the advent of antibiotics and partly because the nature of bacteriophages was not appreciated. However, Eastern Europe and the former USSR (Georgia) continued to employ phages as therapeutic agents for a number of diseases. Their efficacy has, however, never been the subject of controlled studies, and the results of those studies have not been subject to critical evaluation by publication in peer-reviewed scientific journals.
In a very preliminary pilot study, conducted under ISTC Grant # 1176-2p, it was shown that a phage lytic for Burkholderia mallei was very effective in curing mice from infection and, in fact, a single treatment with phage appeared more effective than a single dose of antibiotic administered to acutely infected animals.
The experiments described in this proposal attempt to confirm and extend this pilot study using the same phage isolate. The experience of those most familiar with phage therapy is that a combination of different phages within a single cocktail is more effective than the use of a single phage. Therefore, it is also planned to test new lytic phages, and bacteriophage virulent for B. mallei phage (recently isolated from B. thailandensis E125 and described by Woods et al. from USAMRIID) for their therapetic use.
We will also test lytic phage-encoded enzymes as novel antibiotics (as recently demonstrated by Fischetti and coworkers for streptococcal and anthrax infection) against B. mallei.
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