Brandon Jutras has been researching the Lyme disease-causing bacteria Borrelia burgdorferi for over 12 years. By focusing on basic molecular and cellular questions about how the bacterium works, Jutras and his lab aimed to address functional medicine aspects of basic diagnostics, prevention, and treatment. Now, Jutras’ team is one of 10 Phase 1 winners that have advanced to Phase 2 of the LymeX Diagnostics Prize, a prize competition to accelerate the development of Lyme disease diagnostics.
Through September 2023, the Phase 2 cohort is participating in a virtual accelerator designed to help them refine their concepts for detecting active Lyme disease infections in people. The goal of the multiphase LymeX Innovation Accelerator (LymeX) competition is to nurture the development of diagnostics toward Food and Drug Administration (FDA) review.
We spoke with Virginia Tech Assistant Professor Brandon Jutras to understand how the team is homing in on a unique molecular biomarker, addressing diagnostic accessibility, and considering how their research could be applied to other infectious diseases.
Your team has been focused on Lyme disease for several years. How have you applied your research to developing a diagnostic for active infection?
Jutras: “The Cohen Foundation let me know about this competition, and that’s when we started to formulate the team from folks we’ve been working with here for a while on various aspects of Lyme disease glycobiology. The team is a specialized group of experts in glycobiology.
The LymeX Diagnostics Prize was serendipitous, because we were interested in a particular molecule—peptidoglycan—to understand how people can continue to be sick after they’ve been treated. We figured out that peptidoglycan is really unique.
All bacteria have something called peptidoglycan, but B. burgdorferi’s peptidoglycan is highly unusual. The second the bacteria that causes Lyme disease gets in your body through the bite of a tick, they have to grow to cause disease. They’re replicating just like any bacteria does. And as they do that, they spit out peptidoglycan; think of peptidoglycan as a scaffold or a big internal envelope. To grow, they have to expand this envelope or this bag. It resides inside of them. And instead of reusing these pieces, they just spit it out into their environment.
They’re constantly spitting out this highly unusual molecule that’s required for them to survive, but they continually remake it. So, you have something that is extremely unique and incredibly abundant; they make a lot of it, they spit out a lot of it, and no other bacteria has a molecule like this. That then becomes a signature that the bacterium is inside of you and it’s replicating.
We’ve developed a way to detect that molecule. In theory, that should allow us to be able to detect Lyme disease within hours after it’s been transmitted from a tick. It would be, in theory, a perfect biomarker for Lyme disease diagnostic purposes. We can track this molecule by injecting it into animals and fluorescently track it. When we do that, we see that it gets shed in urine within the first couple hours.
The other exciting part of it is we are not trying to detect a protein or DNA, they will be somewhat limiting in terms of molecules per bacterial cell. Peptidoglycan makes up about 15% of all of the bacterium in terms of dry weight. So it’s one of the most abundant molecules that you could possibly try to detect and so it should be very easy to detect it. And then, because it’s so unique, we can make the test really, really specific.”
Current FDA-approved testing relies on the presence of antibodies and can only be used accurately four to six weeks after infection. How is your team considering how to broaden access to testing?
Jutras: “Blood, serum, and urine are our primary biofluids that we’re interested in. In theory, this molecule would persist for at least the first two weeks of infection. Right now, we’re tackling proof of principle, understanding when it works, and when it doesn’t work. Our false negative and false discovery rates are obviously important things to consider. But as far as the test goes, the output should be as simple as a COVID-19 PCR test with a 48-hour turnaround.
Hopefully long term, we can do exactly what happened with COVID-19 and turn it into an at-home test. You wouldn’t be able to do a blood test; that’s not safe. But where we would optimize this is the urine test.”
Through an open innovation model, the LymeX Diagnostics Prize is helping teams overcome diagnostic development barriers, providing funding and technical assistance while fostering cross-disciplinary collaboration. What is most exciting about participating in the competition?
Jutras: “Hearing the different approaches and how everybody’s tackling this from a variety of different angles. We always say that no complicated problem is ever solved using a single approach or a linear approach. It’s helpful to understand the needs and the wants of people, understand what’s available and what folks are looking for, and then also be appreciative of the creativity of the other teams in the competition and how they’re thinking about this. It’s great because the more tests that we have, the better they are and the better we’re all going to be. As we know, prompt diagnosis is the most critical parameter to patient outcomes.
What we’re really trying to focus on right now is understanding the performance of the tool that we have and how we can improve it. We never want it to fail when someone is infected and we never want it to be wrong when they’re not. That’s where we’re focusing all of our efforts right now, because you can imagine some of these procedures require about two dozen or so different steps. And every one of those steps, you could try a hundred different parameters, so there are a lot of permutations or possible combinations of things to try and improve either the sensitivity or the specificity.”
Much of your team’s work has been on the pathogenesis of Lyme disease, or how infection progresses to disease. Outside of your progress in the LymeX Diagnostics Prize, what are you looking at?
Jutras: “There are so many fundamental things that we don’t understand about how this bacterium works, how it even replicates itself. Once it replicates itself, how does it actually cause disease? Bacterial pathogens that cause severe infections often have signatures that we know are associated with the infection, like a toxin or a particular product that we know is responsible for driving a particular symptom. With the bacterium that causes Lyme disease, they have none of those things. How we go from being bitten by a tick to having severe, debilitating illness is almost entirely unknown.
The lab asks fundamental questions about how this bacterium performs basic tasks, and uses that information to understand how it is causing disease and how we can intervene. We do everything from cell biology to studying peptidoglycan in the context of Lyme arthritis.
In patients that have Lyme arthritis, we can detect this molecule in their knee joints. That’s after these patients have been treated with oral and IV antibiotics, but still have inflammation in their knees. So we’re using this molecule to understand the disease progression process. And then another important feature is that this molecule is the largest target for antimicrobials. Penicillin, cephalosporin, and all their derivatives: They all target the synthesis of peptidoglycan, and so we’re also working on different aspects of therapeutics as well.”
As you’ve noted, your lab has homed in on a unique biomarker for Lyme disease diagnostics. Could these findings be applied to diagnostics innovation more broadly?
Jutras: “Immuno-PCR and other methods we’re using to detect peptidoglycan could certainly be applied to other biosignatures in other infectious diseases in which the bacterial load is low. The principle—as long as you have the right target, and you have a really sensitive and specific way to detect that target—should be transferable across basically any type of bacterial infection where the diagnostics are less than optimal.”
Looking ahead: Expert judging panel to convene in October 2023
Following the accelerator, the cohort will submit concept papers that detail solution refinement, clinical and patient input, and a roadmap from lab to market. The competition judging panel—composed of experts across biology, clinical and technology translation, patient experience and advocacy, diagnostic science and technology, exponential innovation, and ethics—will evaluate eligible submissions according to official Phase 2 evaluation criteria. Based on the judges’ evaluations, the panel will recommend up to five Phase 2 winners of the LymeX Diagnostics Prize.
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