The Lyme disease pathogen Borrelia burgdorferi has an unusual ability to substitute manganese for iron to build enzymes, which helps it elude immune defenses as well as tests to detect it. 

Introduction

There’s something about the pathogen that causes Lyme disease that makes it hard to diagnose and treat. Borrelia burgdorferi is a species of spiral bacteria that somehow eludes the body’s immune defenses. Standard tests don’t detect its presence.

This bacteria is transmitted to humans via tick bites. Over the past two decades, the number of infected ticks has skyrocketed. Hundreds of thousands of people suffer from Lyme disease every year. Symptoms include rashes, fever, chills, headaches, fatigue, sweating, dizziness, tremors, and muscle and joint pain. Untreated, these disabling symptoms can persist or resurface for years.

A key way to prevent long-term problems is to start treatment in the critical early stages of infections. But many different medical conditions can cause similar symptoms. Without a valid way to home in on B. burgdoferi, doctors can overlook Lyme disease. Or worse, they can misdiagnose and futilely treat the wrong ailment.

 

The Strategy

So what makes B. burgdorferi different from other bacteria? The answer, as Sherlock Holmes might put it, is elemental. Bacteria typically use iron to make enzymes that they need to grow and function. But scientists have found that Lyme disease-causing bacteria has evolved to substitute iron’s next-door neighbor on the periodic table: manganese.

Unlike most bacteria, B. burgdorferi doesn’t need iron to grow. In standard detection tests, blood, urine, or other samples are cultured in labs to grow bacteria and reveal their presence. But iron-free B. burgdorferi doesn’t grow well in these tests and evades detection.

Instead, Lyme disease tests rely on detecting the presence of antibodies that the body makes to fight bacteria. But it can take a while to produce antibodies. They can also linger from older or different illnesses. So results from Lyme disease antibody tests aren’t very timely, accurate, or easy to interpret.

The Lyme disease-causing bacteria’s manganese substitution also helps it dodge immune system defense mechanisms. One such mechanism is that the body makes chemicals that inhibit the gut from absorbing iron and sending it into the bloodstream. That makes us anemic, which is why we feel tired and weak when we’re sick. But it also effectively starves most pathogens of the iron they need to build enzymes.

But not B. burgdorferi. It can continue to make enzymes with manganese instead of iron. Some of these enzymes protect them against another immune defense. The body bombards bacteria with superoxide radicals. These highly reactive molecules damage most bacteria. But B. burgdorferi makes manganese enzymes that neutralize superoxides.

The Potential

The discovery opens new avenues to look for novel ways to detect and fight Lyme disease. Humans do not have manganese-containing enzymes. So any therapies that target those enzymes would be effective on B. burgdorferi and safe for people. Additionally, it shows an example of the advantage gained by an organism when it can swap out a resource that other organisms depend on and that  is commonly targeted by both defensive and offensive processes.

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Deer ticks (Ixodes ricinus) transmit the Lyme disease‑causing bacteria Borrelia burgdorferi

Image: National Institute of Allergy and Infectious Diseases, National Institutes of Health / CC BY NC SA - Creative Commons Attribution + Noncommercial + ShareAlike

The Lyme disease spirochete, Borrelia burgdorferi, is an obligate parasite that cycles between ticks and vertebrate hosts. B. burgdorferi alters the proteins expressed on its outer surface, depending on the state of each host. Here, we used immunofluorescent antibodies to identify spirochetes that express outer surface protein D (yellow and red) and merged the image with an image of all the spirochetes labeled with an anti‑B. burgdorferi antibody (green).

Last Updated September 16, 2020