Mycobacteriophages: Cornerstones of Mycobacterial Research

This chapter describes the ways that a systematic use of phages led to the development of novel cloning vectors and ultimately transformation of mycobacteria. In addition, it describes how the detailed characterization of one phage, L5, has provided an abundance of novel insights into and genetic tools for mycobacterial molecular genetics. Lastly, it also describes how the combination of a reporter gene with a mycobacteriophage has breathed new life into rapid assessment of drug susceptibilities in clinical samples of Mycobacterium tuberculosis and is also providing a useful tool for screening novel antituberculosis compounds. Mycobacteriophage L5 is the best characterized of the mycobacteriophages. L5 lysogens of M. smegmatis contain a copy of the L5 prophage integrated site specifically into the bacterial chromosome. The introduction of the BACTEC system for clinical analysis of M. tuberculosis has considerably shortened the time needed for drug susceptibility determination. Luciferase reporter mycobacteriophages have the potential of greatly reducing the time needed for M. tuberculosis analysis in a simple and relatively inexpensive assay. The attractions in using luciferase reporter phages for drug screening are many. First, they can provide a readout of results in as little as 2 h. Second, they can be easily adapted to an automated system that uses microtiter plates. The finding of even a single new antituberculosis drug could have an important impact on the control of tuberculosis, and the authors believe that the search for such a drug warrants efforts to develop luciferase reporter antibiotic screening systems for M. tuberculosis.