Exploring the unique characteristics of Lyme bacteria

When you take a look at the career of microbiologist George Chaconas, there’s a clearly identifiable moment when the focus of his research abruptly shifted from the study of one fairly obscure organism to another.

Prior to 1999, Chaconas spent much of his time concentrating on the bacteriophage Mu, a strange hybrid of an organism that combines the elements of a virus with those of a transposon (a so-called “jumping” gene), allowing Mu to exist as both a freakishly mobile DNA sequence that can change location within a genome and a virus capable of infecting E. coli bacteria.

Then something intriguing happened.

Chaconas was introduced to an even more bizarre organism that came in the form of Borrelia burgdorferi, the primary cause of Lyme disease in North America. Chaconas, it turns out, is a scientist who is drawn to quixotic lifeforms. So in 1999, he abruptly switched his focus and, with the help of a prestigious Guggenheim Fellowship, took a sabbatical from his laboratory at the University of Western Ontario (now Western University) to spend a year at the US National Institutes of Health’s famed Rocky Mountain Laboratories in Montana (where Borrelia burgdorferi was first identified as the organism at the root of Lyme disease), getting up to speed on this unusual bacterium and learning how best to grow and genetically manipulate it.

What attracted Chaconas to Borrelia burgdorferi were some unique features that set it apart from every other organism the former Canada Research Chair in the molecular biology of Lyme borreliosis (2003 to 2017) had encountered. Those features include a segmented genome and linear chromosomes that sport hairpin ends, neither of which are typical in a bacterium. Borrelia burgdorferi also boasts another anomaly not seen in any other known pathogen: It does not require iron to exist.

Chaconas’s research at the University of Calgary, where he is currently a professor in the Department of Biochemistry & Molecular Biology and Microbiology, Immunology & Infectious Diseases, focuses on three main areas.

The first is antigenic variation, a curious mechanism that allows Borrelia burgdorferi to alter its external structure into a billion or so variants (that’s not an exaggeration) so that the immune system isn’t able to recognize it as an invader. This allows a Lyme infection to rampage through a body relatively unchecked. The molecular mechanism that governs Borrelia burgdorferi’s ability to vary its antigens to such a degree remains unclear, something that Chaconas is determined to change. Over the years that has resulted in him identifying two enzymes that Borrelia burgdorferi requires to alter its outer surface proteins, both of which represent possible targets for the future development of novel drugs that will hopefully move us away from the use of antibiotics in the treatment of Lyme disease.

Chaconas also investigates how exactly Borrelia burgdorferi goes about regulating the roughly 150 genes that allow it to successfully move from a host tick to a mammal, a genetic magic act that's imperative for the bacterium to survive in two highly different creatures with dramatically different immune systems.

A third area of research involves nailing down the process that Borrelia burgdorferi uses to enter and leave blood vessels as it moves around the body in an effort to colonize various tissues including those of the joints, organs and nervous system. Chaconas’s early research looked into how Borrelia burgdorferi manages to escape fast-flowing blood and adhere to blood vessel walls. He later progressed to nailing down how the bacterium escapes blood vessels once it has successfully adhered to them.

The one-time Canadian Lyme Disease Foundation board member studies this complicated, multistage process using intravital microscopy, which allows him to see individual Borrelia burgdorferi bacteria — which have been dyed fluorescent green or red — doing their thing in real-time inside live mice. This technique allows Chaconas to watch what the bacteria are doing as they are doing it.

During his more than 20 years of research, Chaconas has entered into many collaborations with other scientists. One recent collaborator is Ian Lewis, a biochemist at the University of Calgary and an expert in the field of translational medicine. Together they’re working on developing tests that will detect metabolites in the bloodstream that signal the presence of a Borrelia burgdorferi infection. The goal of this research is to move us away from the controversial indirect antibody tests currently being used to detect Borrelia burgdorferi in people suspected of having Lyme disease. Current testing lacks sensitivity during the first few weeks after infection when Lyme disease is at its most treatable. It also can’t determine whether Borrelia burgdorferi remains active in a patient who has been treated for Lyme disease, which means we are presently unable to say whether someone who continues to express symptoms consistent with Lyme disease is still battling an active Borrelia burgdorferi infection or is sick for another reason.

This article was first published in Issue 29 of The Lyme Report and updated July 18, 2023.