Sat. Jan 22nd, 2022

Tanner DeHart and Brandon Jutras

image: Tanner DeHart and Brandon Jutras are two of the researchers who discovered the unique bacterial property. Photo by Alex Crookshanks for Virginia Tech.
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Credit: Virginia Tech

You do not have to go far to find ticks. Just go outside and look for some grass. Look at the top of the shiny, green blade – usually ankle high. There may be a tick waiting.

If something that breathes abuts the grass, the tick takes something resembling a needle – called its hypostome, which has dozens of fishing hook barbs – and inserts it into the skin. If it is not noticed, Lyme disease can be transmitted to the host after approx. 24 hour feeding.

Virginia Tech researchers discovered that the bacterium that causes Lyme disease has a very unusual modification in its protective molecular bag – its peptidoglycan, which is common to all bacteria.

The change in this bacterium is unprecedented – it is an unusual sugar modification that is not known to occur in any organism. One way the bacterium gets this sugar modification is from ticks by absorbing a carbohydrate that is unique to ticks. The change is specific to ticks and allows the bacterium to move better and be more likely to cause disease.

“We believe this change is crucial to how the bacterium causes disease and is something we can utilize for both therapeutic and diagnostic purposes,” said Brandon Jutras, assistant professor of biochemistry at the College of Agriculture and Life Sciences and an affiliated faculty member. Fralin Life Sciences Institute and Center for Emerging, Zoonotic and Arthropod-Born Pathogens.

The results were recently published in Nature Microbiology, which is produced by the Nature Portfolio, and the research is the result of four years of work with ticks and lyme disease, for which Jutras has received great praise.

“Participating in this research was the most engaging and rewarding experience of my academic career at Virginia Tech,” said lead author Tanner DeHart ’20 and ’21, who took his bachelor’s and master’s degree in biochemistry at Virginia Tech and is now a Ph.D. D. . students at Harvard University. “This opportunity gave me the opportunity to hone my scientific skills, develop myself as a more independent researcher and gain first-hand experience with many experimental techniques and designs.”

Over the past two decades, the United States has experienced a dramatic increase in both the number of reported cases and the geographic distribution of Lyme disease. In the state of Virginia, the disease is transmitted by the bite of black-legged ticks, which are infected with the Lyme disease-causing bacterium Borrelia burgdorferi.

In 2019, Jutras discovered it B. burgdorferi secretes peptidoglycan when it invades the human body. Although all bacteria have peptidoglycan, many do not release the drug.

The bacterium that causes Lyme disease is different. It has peculiarities in how it produces its peptidoglycan and its components.

Years ago, scientists were unable to figure out these oddities. They had huge chunks of missing information. After four years of research, they found a few of the missing puzzle pieces. Although they do not know how the bacterium makes this modification, they know how the bacterium acquires it.

The sugar there B. burgdorferi putter in its peptidoglycan is a degradation product of chitin, a structural carbohydrate with bound sugar molecules made from modified glucose. Chitin is a critical component in fleets.

“The remarkable thing here is that the bacteria that cause Lyme disease suck a decomposition product out of its tick vector and use it to help make this unusual molecule,” said Jutras, also an affiliate of the Translational Biology, Medicine, and Health Graduate Program. at Virginia Tech. “What’s more fascinating is that the bacterium appears to have developed this fine-tuned adaptation to make it move efficiently, which is a trait required for disease.”

This adaptation makes the bacteria one of the fastest organisms on the planet in terms of how it can move.

From a technical point of view, the identification of the sugar, the chitobiose – the degradation product of the chitin core – was in the research and discovery.

To determine that chitobiosis was the actual sugar, the researchers performed LCMS, liquid chromatography combined with mass spectroscopy in The Mass Spectrometry Research Incubator (VT-MSI), directed by Rich Helm, of the Fralin Life Sciences Institute’s Core Services. They also performed nuclear magnetic resonance and metabolic labeling studies with C13-labeled sugars to confirm the identity of unusual modification.

In doing so, they found out why the bacterium has this modification.

The road B. burgdorferi movements are by spiraling – or twisting – their own body using the flagellum. The flagellum is essentially a propeller, but on the outside of the bag. The propeller swings against this large molecular bag, and as a result, it propels itself forward. This type of strategy allows them to move through muscle tissue, even cartilage, relatively easily.

Why is sugar modification so important? This allows the bag to be more flexible and withstand the torque.

The team used nuclear force microscopy to examine the elasticity of the peptidoglycan.

“The material is much more flexible and resilient in the sense that they can propel themselves,” Jutras said. “If they do not have that modification, the material becomes much stiffer and the ability to move is impaired.”

Previously, one had a theory that this bacterium should be flexible, but one never knew how or why.

“We need to understand this mechanism because it would be a perfect target for therapy,” Jutras said. “We know one way – when it’s at the crossroads. But how does it make this modification when it is in a human? There is minimal or no chitin in a human. When we impair the bacterium’s ability to absorb chitobiosis, they still have this modification. There’s just a lot less of it. “

This means that the bacterium has a different way of making this modification in its peptidoglycan. Understanding how the bacterium makes this modification inside a human is the next step in research – and Jutras and his team are already studying this path.

In the state of Virginia, the disease is transmitted by the bite of black-legged ticks, which are infected with the borreliosis-causing bacterium Borrelia burgdorferi. Photo by Max Esterhuizen for Virginia Tech.

A long and winding road

Jutras’ previous research has shown that peptidoglycan in B. burgdorferi lingers in the body of Lyme arthritis patients after the bacteria have entered the body. Weeks to months after the first infection, the peptidoglycan remains, which stimulates inflammation and pain.

The laboratory discovered a protein associated with the peptidoglycan of Borrelia burgdorferi which plays an amplifying role in causing inflammation in Lyme arthritis patients by acting as a molecular beacon that counteracts patients’ immune systems.

The new discovery by Jutras and his team may explain why the peptidoglycan can hang out and cause arthritis in Lyme patients. Human bodies cannot process the peptidoglycan B. burgdorferi just as it can trillions of bacteria in and on human bodies.

“From a bacteriologist’s perspective, this is a paradigm shift in how we understand peptidoglycan, an essential molecule produced by virtually all bacteria and the most common antibiotic target,” Jutras said.

Since almost no other bacteria have peptidoglycan quite like B. burgdorferi, it is an attractive biomarker for diagnostics. Biomarkers are unique molecular signatures, like hashtags that serve as an indicator that something has gone wrong in a system and are often used to diagnose various types of cancer.

This previous research and discovery led directly to the discovery of the self-changing properties of B. burgdorferi and its potential diagnostic methods. The new research opportunities are focused on this very unusual molecule and the bacteria that secrete these molecules.

“As diagnostics goes, it is an exciting new area of ​​research for the laboratory as it relates to this discovery because this is a very unusual molecule,” Jutras said. “The bacterium secretes these molecules, and this discovery could lead to the development of a diagnostic tool that focuses on detecting this unusual molecule, like a biomarker for lyme disease. An approach that could make the diagnosis of lyme disease as simple as a COVID-19- quick test. “

The unraveling of the mystery of the most reported vector disease in the country is progressing.

In the meantime, do not stop performing these cross checks.

The research is made possible by the Steven & Alexandra Cohen Foundation, the National Institutes of Health and the Bay Area Lyme Foundation.

Citation: DeHart, TG, Kushelman, MR, Hildreth, SB et al. The unusual cell wall of borreliosis spirochaete Borrelia burgdorferi is shaped by a tick sugar. Nat Microbiol 6, 1583-1592 (2021). https://doi.org/10.1038/s41564-021-01003-w


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