Bacteriophages such as the Escherichia coli phage Lambda have been studied extensively for several decades as model systems for the study of such topics as gene regulation, host-virus interactions, and macromolecular assembly. We have taken advantage of the base of information about Lambda and related phages for two purposes: (1) Detection of mutagens and carcinogens: We developed a novel assay for the detection of mutations in a Lambda transgene contained in mice. The assay selects for phage containing forward mutations only in the Lambda cII gene, using a mutant (hfl) Escherichia colihost. In addition to the relative ease of direct selection, the sensitivity of this assay for both spontaneous and chemically induced mutation was comparable to the widely used mutational target gene lacI. Moreover, our assay costs 80 times less to use than the lacIsystem. Our cII assay system is now being used worldwide as a replacement for the lacIsystem. In a collaboration with Dr. Glenn Merlino, the system is now being used to study the role of mutagenesis in cancer development and it appears that expression of the new gene causes a change in the spectrum of mutations(2) Bacteriophage therapy: 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 the capacity of mammalian host defense systems to remove phage particles from the circulatory system. In our studies involving bacteremic mice, to reduce phage elimination by the host defense system, we previously isolated E. coli phage Lambda and Salmonella phage P22 mutants able to remain in the circulatory system for longer periods of time and also have greater capability as antibaceterial agents in animals infected with lethal doses of bacteria. The mutations in Lambda are in the gene for the major capsid protein. In a collaboration with Dr. Carl Merril and Dr. Dean Scholl, we have now isolated and characterized a DNA bacteriophage capable of infecting pathogenic Escherichia coliwith K antigens. The phage, fK1-5, ulike previously isolates, contain two types of tails enabling it to grow on both hosts with K1 and K5 antigens.
| Bair, Catherine L; Oppenheim, Amos; Trostel, Andrei et al. (2008) A phage display system designed to detect and study protein-protein interactions. Mol Microbiol 67:719-28 |
| Edgar, Rotem; McKinstry, Michael; Hwang, Jeeseong et al. (2006) High-sensitivity bacterial detection using biotin-tagged phage and quantum-dot nanocomplexes. Proc Natl Acad Sci U S A 103:4841-5 |
| Adhya, Sankar; Black, Lindsay; Friedman, David et al. (2005) 2004 ASM Conference on the New Phage Biology: the 'Phage Summit'. Mol Microbiol 55:1300-14 |
| Rao, Srinivas; Hu, Stella; McHugh, Louise et al. (2005) Toward a live microbial microbicide for HIV: commensal bacteria secreting an HIV fusion inhibitor peptide. Proc Natl Acad Sci U S A 102:11993-8 |
| Scholl, Dean; Adhya, Sankar; Merril, Carl (2005) Escherichia coli K1's capsule is a barrier to bacteriophage T7. Appl Environ Microbiol 71:4872-4 |
| Vitiello, Christal L; Merril, Carl R; Adhya, Sankar (2005) An amino acid substitution in a capsid protein enhances phage survival in mouse circulatory system more than a 1000-fold. Virus Res 114:101-3 |
| Scholl, D; Kieleczawa, J; Kemp, P et al. (2004) Genomic analysis of bacteriophages SP6 and K1-5, an estranged subgroup of the T7 supergroup. J Mol Biol 335:1151-71 |
| Merril, Carl R; Scholl, Dean; Adhya, Sankar L (2003) The prospect for bacteriophage therapy in Western medicine. Nat Rev Drug Discov 2:489-97 |
| Gupta, Amita; Onda, Masanori; Pastan, Ira et al. (2003) High-density functional display of proteins on bacteriophage lambda. J Mol Biol 334:241-54 |
