Thursday, September 10, 2009

Phage Hunters

18 freshmen students have enrolled in my Genomics Research Experience course aka Phage Hunters. This course is supported by the Howard Hughes Medical Institute's Science Education Alliance. My students have begun the process of isolating novel Mycobacteriophages by collecting soil samples from the wild and plating them on lawns of Mycobacterium smegmatis, a M. tuberculosis relative. Unlike M. tuberculosis, M. smegmatis is non-pathogenic and is easier to grow and manipulate under experimental conditions. Nonetheless, by virtue of their close phylogenetic relationship, the two bacteria are quite similar in many respects. Thus, M. smegmatis may be an excellent model for deriving treatments against tuberculosis.

Collecting Mycophage is already paying handsome dividends. Albert Einstein College of Medicine Professor William Jacobs isolated a phage he named the Bronx Bomber from soil from his own backyard in the Bronx. With University of Pittsburgh Professor Graham Hatfull, Jacobs characterized this phage in the laboratory. They found that this phage is able to insert itself into the genome of M. smegmatis at a very specific location in the groEL1 gene, thus disabling the gene. One of groEL1's functions is to facilitate the production of biofilms.

Biofilms are extracellular polymeric substances that aid and protect microbes. They allow bacteria to persist in the face of antibiotics. It's estimated that 80% of infections involve biofilm formation. While biofilm formation in tuberculosis has not yet been uneqivocally confirmed, M. tuberculosis does have a groEL1 gene with 90% similarity to that of M. smegmatis.

If the phage is able to infect M. tuberculosis or is mutated to infect M. tuberculosis, it is possible that some day the phage could be used as therapy against tuberculosis. As one of the three primary diseases of poverty, tuberculosis has a devastating impact in the developing world.

Top Photo: Bxb1 is a mycobacteriophage that was originally isolated from Dr. Jacobs' backyard in the Bronx. It is affectionately called "The Bronx Bomber" as it forms large plaques on a plate with lawn of Mycobacterium smegmatis cells (left panel). The Bxb1 phage plaques are characterized with their clear centers surrounded by turbid rings. The turbid rings represent lysogens (i.e. M. smegmatis bacterial cells into which Bxb1 has integrated) of M. smegmatis that are resistant to superinfection with Bxb1 phage. These lysogens are defective in biofilm formation. A transmission electron micrograph of Bxb1 is shown in the right panel. Courtesy of Jordan Kriakov, William R. Jacobs, Jr.

Middle photo: Image shows Mycobacterium smegmatis growing as a biofilm on a liquid surface, with its characteristically textured folds. Courtesy of Anil Ojha, Tom Harper, Graham Hatfull.


  1. Does the most recent cell to join a biofilm get protection from antibiotics (e.g., due to collective production of antibiotic-degrading enzymes), or does it rely on other cells joining on top of it, forming a barrier? -- Ford

  2. Not just for therapy, mycobacteriophages are providing tons of data points for evolutionary studies.

    The number, diversity, and constant flux of this population is a great model system for learning how genes change and move in a population!