Joe Harrison: Bugs-to- Drugs and Antibiotic Resistant Microorganisms

When you first meet Joe Harrison you are immediately struck by both his kind nature and obvious passion for his research.  The research that Joe conducts at the University of Calgary focuses on the study of surface-attached bacterial communities called biofilms, and how infectious bacterial biofilms resist antibiotic therapy.  Over the last five years Joe and his lab have worked towards two major breakthroughs, breakthroughs that they continue to pursue with a veracious scientific appetite.  The first was a major research initiative called Bugs-to-Drugs, which focuses on using naturally occurring microorganisms to defeat antibiotic resistant bacteria; the second was the discovery of how certain bacteria feel heat and how they adapt to a person’s thermal body temperature to make individuals sick. 

Joe describes Bugs-to-Drugs as a fairly simple research initiative that uses the naturally occurring competition of bacteria within our bodies to produce microbes to assist in fighting antibiotic resistant superbugs.  Joe states:

“Within your body live thousands of different microorganisms which have evolved to compete with one another.  These microorganisms have a natural capacity to produce antibiotics, which is how these bacteria compete with each other.  We have thought for some time that this is one of the least explored areas of microbiology on the planet, and we have discovered numerous things from the human body and other environments that produce molecules similar to antibiotics, which we are using to help fight superbugs.”

By harnessing the naturally occurring antibiotics used by the bacteria in our bodies Joe’s lab is working to find new methods to kill harmful bacteria that not only make individuals sick, but if left untreated could lead to antibiotic resistant superbugs that have harmful impacts on a global scale.  Joe hopes that the Bugs-to-Drugs initiative can be used to combat this global threat, as some of the molecules developed in his lab could potentially “be deployed on a global scale to eliminate antibiotic resistance.  The World Health Organization put together a list of priority pathogens in which new antibiotics of alternative therapeutics are urgently needed, and Bugs-to-Drugs specifically targets the top organisms on this list to help with this issue.”   This global thinking shows the ambition of both Joe and his lab, as he is aiming to not only positively impact his local community, but help as many people effected by antibiotic resistant organisms as possible. 

In addition to discovering new methods of killing superbugs, Joe hopes to rescue existing antibiotics through the use of adjuvants.   Adjuvants work by blocking the antibiotic resistance of a superbug, making the harmful bacteria susceptible to the attack of antibiotics.  Joe describes the function of adjuvants, saying “adjuvants work by blocking antibiotic resistance, after they [block a harmful organisms resistance to antibiotics] an antimicrobial resistant organism is again sensitive to an antibiotic and can be killed.”  If the harmful organism were holding a shield, the adjuvant removes this shield so that the antibiotic can kill the organism and the individual can recover from being sick.  Joe speaks of the purpose of the molecules created in his lab in relation to these harmful bacteria, and why these molecules are so important in the fight against antibiotic resistant organisms and adjuvants.  “The process works a lot like counter resistance, to use a war metaphor.  If you have a bacterium that has developed the capacity to resist a certain antibiotic, our molecule disables that resistance and makes the bacterium vulnerable to attack.”  In the growing fight against antibiotic resistant superbugs it is comforting to know that we have a counter resistance team in the Bugs-to-Drugs initiative, a counter resistance team that is gaining traction and is being led by Joe and his lab.  

One of the major breakthroughs that led to the creation of Bugs-to-Drugs was the discovery by Joe’s lab of how bacteria feel heat, and how certain bacteria use thermal sensation, the ability to feel an individual’s body heat, to turn on genes and proteins that can be used to make a person sick.  What Joe finds fascinating about the proteins of the bacteria involved in this process is that “The bacteria work largely in the same way as proteins that are inside the neurons of our body do; they fundamentally sense hot and cold temperatures in some of the same ways that our body would, the biochemistry is different but some of the underlying principles are similar.”  As is often the case in science, Joe was led to these discoveries largely by accident…

“I had an interest in a process called signal transduction, which is basically a way for a cell to biochemically adjust its physiology to outside stimulus.  I had to shift a bunch of strains that I had built myself in a lab in the United States; I built them in the United States because I did my post-doc in Seattle.  These particular strains were engineered to look a certain way when you grew them when the single transduction pathway was activated or not, and we were trying to understand exactly what these single transduction pathways were responding to.  I had done it unsuccessfully for quite some time, and then I took the strains that I had engineered and shipped them to my lab in Calgary, and they lost the phenotypes.  This is literally the day I’m leaving my lab in Seattle and they lost the look that they normally have on agar.  I thought I had done something wrong, but when we grew them in Calgary again they were fine.  It got me thinking, whenever we moved these strains they lost their particular look and color, and I eventually thought, ‘Oh my god, these things are responding to temperature’.  And that’s how I discovered that these things were reacting to heat, I stuck them in a FedEx envelope and they lost their color.”

It is interesting to think that something as simple as shipping an envelope could lead to ground breaking research and that it is sometimes the unexpected that can pave the way to larger ideas.  It is comforting to know that the fight against antibiotic resistant bacteria and superbugs is in good hands, and that Joe and his lab are keeping a watchful eye on the future of antibiotics and other therapeutics. 

An Article by Glynndon Dobson