Under the leadership of Alexander Ensminger and Beth Nicholson, a collaborative team of researchers has made a truly remarkable discovery. To do this, they’ve discovered a new phage named LME-1. This curious piece of genetic code now resides in a special freezer. It shows every genetic hallmark of a phage and has a very specific target on Legionella pneumophila, the bacteria responsible for Legionnaires’ disease.
LME-1 is an important development for the field of microbiology and for the prevention of Legionella infections. Its structure, like that of many phages, includes an icosahedral head covered with surface proteins, and a short tail. Through digital modeling, we received high-resolution images that exposed its unique structure. Our trans-Atlantic collaboration brought Susan Lea and Justin Deme from the National Cancer Institute, NIH, United States.
For years, Ensminger’s group, as well as other research teams, could not trigger LME-1 to yield a single phage. To prepare them for deep sequencing, their efforts involved a range of typical methods to trigger, or otherwise isolate, phages—all of which failed.
“All of the standard tools for either activating a phage or isolating a phage didn’t work,” – Alexander Ensminger
The breakthrough moment came when they determined how to trigger the previously mysterious genetic switch.
“The ‘aha!’ moment was figuring out how to activate this thing,” – Ensminger
The identification of LME-1 heralds promising new frontiers for phage therapy. In addition, it reveals the molecular mechanisms responsible for Legionnaires’ disease. The lag1 gene, present in about 80% of Legionella isolates, prevents LME-1 from binding to the bacterial cell surface. This important link was recently testified to by Elizabeth Chaney, a Ph.D. student under Ensminger’s direction.
“We have a previously unknown phage to ‘thank’ for Legionnaires’ disease,” – Ensminger
Recognizing this complex interaction is critical, as it uncovers a crucial facet to the pathogenicity of Legionella pneumophila. According to Ensminger, the effort to find new phages that could kill Legionella has taken fifty years.
“The Legionella field has been looking for phages for 50 years,” – Ensminger
Nicholson is currently focusing on creating a “defenseless” version of the bacteria. This new method will greatly advance his search for more phages that might most effectively target Legionella.
“Finding the first phage for Legionella opens the door to one day being able to use phage to control Legionella. It’s still a ways down the road but at least it’s a possibility now,” – Beth Nicholson
This is an exciting find. Ensminger cautions that we’re only just beginning to understand the complex interplay between phages and bacteria in order to leverage phage therapy.
“Our study is also a cautionary tale that, with phage therapy, we need to understand the relationship between phage and bacteria before we deploy it because in some instances, resistance to the phage might make the bacteria more harmful to humans,” – Ensminger