Lyme disease bacteria: strains and symptoms

What causes Lyme disease, and how can we identify the strains and symptoms?
02 July 2021

Interview with 

Justin Radolf, University of Connecticut Health Center


A blue cgi bacteria


Lyme disease is a bacterial infection that causes a range of symptoms, from skin rashes and fevers, to fatigue, joint pains and even neurological problems. And it’s that range of fleeting symptoms, developing over a period of time, that means that Lyme disease can often be overlooked - at least initially.  The condition is also becoming more common, and we’ll hear why later in the programme - but first, we need to find out more about the microbe that causes Lyme disease. Chris Smith spoke to Justin Radolf, a microbiologist from the University of Connecticut…

Justin - Lyme disease is caused by a bacterium in the genus Borrelia. Borrelia are spirochetes - they're elongated, helical, spiral shaped organisms, which is how they get their name. There are approximately 20 species of Lyme disease spirochetes, but only a small number are clearly associated with disease. We don't know what makes some of them more infectious than others, but we know that it ultimately goes back to the genes that they contain. Some species also appear to be able to cause certain forms of disease more often than others. And again, we don't know exactly why that is, but it has to do with the genes.

Chris - And are those different subtypes - are they distributed in different geographies? So if I look in certain countries I will find one particular variant of the Borrelia bacteria that cause Lyme, and if I look in a different geography I might find a different one, and therefore I might see different manifestations of the disease in those places?

Justin - Yes, that actually is correct. So for example in North America there's predominantly one species called Borrelia burgdorferi that far and away causes all the cases. When one looks in Europe, there are several major species that cause different manifestations and they are not distributed equally. One finds some in other countries and some in others, and it's heterogeneous.

Chris - And where in the environment do those organisms hangout?

Justin - They live in wooded areas mostly, though grasslands as well. They live in ticks and in small mammals, often rodents, and they go back and forth between them. That's how they maintain themselves. Humans get infected when they intrude on those cycles. It can happen recreationally. It can happen in terms of where people live; in the northeast United States, for example, a lot of people have their nice houses out in the woods where the cycle is occurring. But we now know it even occurs in urban areas as well.

Chris - So you've got a lifecycle where mice get infected, ticks feed on the mice and they get infected, ticks go on a new mouse and infect that new mouse, and it goes round and round in a circle. So do mice get Lyme disease, then, or are they resistant to it?

Justin - Mice are reservoir hosts, and as a good reservoir host they get infected but they don't get sick. They don't mount an inflammatory response and they don't seem to be able to eliminate the bacterium. So they're persistently infected.

Chris - And how do the bacteria survive in multiple hosts? Because they're going into these mice, and that's arguably a very different environment to then being in the tick, which is a completely different type of animal, and then potentially passing into us as well. So the bacteria have to exist in a whole range of different environments and both make an animal infectious, but also susceptible to being infected, and it's quite complicated. How do they do it?

Justin - Well, actually that is what many of us are studying, because there are regulators of the genes in the bacterium that are turned on and turned off depending on where the bacterium happens to be. If they're in a tick, they actually sense the blood coming in and then they know that it's time for them to move on. And then when they get into the mammal, they actually go through an adaptive process that enables them to survive in the mammal. So it's really quite ingenious what they have evolved to be able to do.

Chris - And when a tick bites a person, just talk us through how the infection is transmitted and then how the infection unfolds in that person.

Justin - Usually it's the nymphal tick that is the stage that feeds on a human. And so that nymph has to have been infected and will have acquired the spirochete in its earlier stage as a larva. So when the nymph eats and the blood starts to come in, the spirochetes sense that; they start to replicate, they start to divide very rapidly, and then they start to actually penetrate the intestine of the tick where they live; and then they go from there into the salivary glands, and they actually penetrate those, and then they are actually able to get into the saliva; and then they hitch a ride into the feeding site, which would be a human, or a mouse - it depends.

Chris - And what happens to the victim - the person who's being bitten?

Justin - Well, initially not much, because what has to happen is the spirochete itself has to establish itself. We know that there are defences that actually try to eliminate the spirochete. The environment in the feeding site also is thought to suppress the immune response in ways that the bacterium can take advantage of. But over the next several days, once they're deposited, that's when they get their foothold, they start to adjust to the new environment. They're also warding off various defences that the host has naturally. And then they start to move on, they start to move laterally. That eventually gives rise to that skin rash called erythema migrans, the bullseye rash. But they also go deep and they start to penetrate blood vessels. That's when they gain access to the bloodstream, and they can disseminate throughout the blood and invade different organ systems: heart, central nervous system, joints, et cetera.

Chris - And produce that range of symptoms, presumably, that Stella was talking about - in a range of different organ systems and at a range of different times.

Justin - Yes. In fact there are components in the bacterium that are actually pretty well known, that the host recognises as foreign. The host then mounts an inflammatory response. That inflammatory response in the tissues can cause symptoms. For example, in certain parts of the heart it can interfere with the conduction system and cause various kinds of heart block; but it also causes systemic symptoms that make people feel muscle aches, tired, headachy, things like that.

Chris - And why is the immune system not able to eliminate the bacteria from the body?

Justin - That's a great question. And we do not fully know the answer. We know that the bacteria actually has its own defences against the host immune system. It has ways of preventing antibodies that the host makes from eliminating it. Part of it may also be because they're very modal. They are much faster moving through tissues in the white blood cells that get into the tissues in response to the presence of the bacterium. And exactly how they can persist in various sites for such long periods of time and not be eliminated is still a very open question.


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