Speaker
Description
Mycobacteriophages are natural predators of Mycobacterium strains. We have gained insights into mycobacteriophage biology through science education programs such as PHIRE and SEA-PHAGES, in which many students have collected over 30,000 phages, half of which infect Mycobacterium. This set of phages isolated on a single bacterial strain (M. smegmatis mc2155) reveals the amazing genetic diversity of the phage population. These phages has provided insights into the mycobacteria and facilitated development of tools that are broadly useful for the Mycobacterium research community. Elucidating phage diversity and development of engineering tools enable first therapeutic phage intervention for treating an M. abscessus infection. We now have received 650 requests for phage evaluation of NTM strains, which we have screened with a phage panel, although the phage repertoire is limited. Most strains are M. abscessus, of which about 50% have smooth colony morphotypes and are rarely killed efficiently by any phages. The other 50% have rough colony morphotypes, and we can identify one or more phages that infect and kill about 50% of these efficiently. To date we have provided phage preparations for clinical treatment of over 50 patients, providing insights into the opportunities and challenges for Mycobacterium phage therapies. However, a serious challenge to broadening therapeutic use is the narrow host preference of the phages and unpredictability of phage infection profiles. This likely arises from a diverse set of integrated prophages prevalent in M. abscessus strains, a rich and varied plasmid repertoire, and an abundance of known phage defense systems in genomic islands.
