Long-circulating bacteriophage as antibacterial agents Export

@article{citeulike:3465988, abstract = {The increased prevalence of multidrug-resistant bacterial pathogens motivated us to attempt to enhance the therapeutic efficacy of bacteriophages. The therapeutic application of phages as antibacterial agents was impeded by several factors: (i) the failure to recognize the relatively narrow host range of phages; (ii) the presence of toxins in crude phage lysates; and (iii) a lack of appreciation for the capacity of mammalian host defense systems, particularly the organs of the reticuloendothelial system, to remove phage particles from the circulatory system. In our studies involving bacteremic mice, the problem of the narrow host range of phage was dealt with by using selected bacterial strains and virulent phage specific for them. Toxin levels were diminished by purifying phage preparations. To reduce phage elimination by the host defense system, we developed a serial-passage technique in mice to select for phage mutants able to remain in the circulatory system for longer periods of time. By this approach we isolated long-circulating mutants of Escherichia coli phage lambda and of Salmonella typhimurium phage P22. We demonstrated that the long-circulating lambda mutants also have greater capability as antibacterial agents than the corresponding parental strain in animals infected with lethal doses of bacteria. Comparison of the parental and mutant lambda capsid proteins revealed that the relevant mutation altered the major phage head protein E. The use of toxin-free, bacteria-specific phage strains, combined with the serial-passage technique, may provide insights for developing phage into therapeutically effective antibacterial agents.}, author = {Merril, C. R. and Biswas, B. and Carlton, R. and Jensen, N. C. and Creed, G. J. and Zullo, S. and Adhya, S.}, citeulike-article-id = {3465988}, citeulike-linkout-0 = {http://www.pnas.org/content/93/8/3188.full.abstract}, citeulike-linkout-1 = {http://www.pnas.org/content/93/8/3188.full.full.pdf}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/8622911}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=8622911}, day = {16}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {circulating, long, phage}, month = {April}, number = {8}, pages = {3188--3192}, posted-at = {2008-10-30 15:40:38}, priority = {2}, title = {Long-circulating bacteriophage as antibacterial agents}, url = {http://www.pnas.org/content/93/8/3188.full.abstract}, volume = {93}, year = {1996} }

TY - JOUR ID - citeulike:3465988 L3 - citeulike-article-id:3465988 N2 - The increased prevalence of multidrug-resistant bacterial pathogens motivated us to attempt to enhance the therapeutic efficacy of bacteriophages. The therapeutic application of phages as antibacterial agents was impeded by several factors: (i) the failure to recognize the relatively narrow host range of phages; (ii) the presence of toxins in crude phage lysates; and (iii) a lack of appreciation for the capacity of mammalian host defense systems, particularly the organs of the reticuloendothelial system, to remove phage particles from the circulatory system. In our studies involving bacteremic mice, the problem of the narrow host range of phage was dealt with by using selected bacterial strains and virulent phage specific for them. Toxin levels were diminished by purifying phage preparations. To reduce phage elimination by the host defense system, we developed a serial-passage technique in mice to select for phage mutants able to remain in the circulatory system for longer periods of time. By this approach we isolated long-circulating mutants of Escherichia coli phage lambda and of Salmonella typhimurium phage P22. We demonstrated that the long-circulating lambda mutants also have greater capability as antibacterial agents than the corresponding parental strain in animals infected with lethal doses of bacteria. Comparison of the parental and mutant lambda capsid proteins revealed that the relevant mutation altered the major phage head protein E. The use of toxin-free, bacteria-specific phage strains, combined with the serial-passage technique, may provide insights for developing phage into therapeutically effective antibacterial agents. IS - 8 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 3192 TI - Long-circulating bacteriophage as antibacterial agents VL - 93 SP - 3188 KW - circulating KW - long KW - phage AU - Merril, CR AU - Biswas, B AU - Carlton, R AU - Jensen, NC AU - Creed, GJ AU - Zullo, S AU - Adhya, S PY - 1996/04/16/ UR - http://www.pnas.org/content/93/8/3188.full.abstract ER -