Use of Bacteriophages to Prevent, Diagnose, and Treat Diseases

Adhya, Sankar

Abstract

Use of bacteriophages to prevent, diagnose and treat diseases.Bacteriophage infection. In order to understand the specificities of various phages for use in the detection or treatment of bacterial infections, we have studied the cellular targets of phage infections using several phages. The study with phage lambda has been completed. The poles of bacteria exhibit several specialized functions related to the mobilization of DNA and certain proteins. To monitor the infection of Escherichia colicells by light microscopy, we developed procedures for the tagging of mature bacteriophages with quantum dots. Surprisingly, most of the infecting phages were found attached to the bacterial poles. This was true for a number of temperate and virulent phages of E. colithat use widely different receptors and for phages infecting Yersinia pseudotuberculosis and Vibrio cholerae. The infecting phages colocalized with the polar protein marker IcsA-GFP. ManY, an E. coliprotein that is required for phage lambda DNA injection, was found to localize to the bacterial poles as well. Furthermore, labelling of lambda DNA during infection revealed that it is injected and replicated at the polar region of infection. The evolutionary benefits that lead to this remarkable preference for polar infections may be related to lambda's developmental decision as well as to the function of poles in the ability of bacterial cells to communicate with their environment and in gene regulation.Use of phage to identify drug targets. We have continued our efforts to identify targets of HIV virions using our previously developed Phage lambda based 2-hybrid system. We have cloned 5 of the major coat proteins of HIV and so far identified 3 pairs of interacting proteins in HIV virions. We are setting up a high-throughput screening procedures.