Friend or Foe? Tick Research Blurs Pathogen-Symbiote Line

A tick waits for passing prey on a blade of grass. (Credit: Matt Pinski)

(CN) — One species’ pathogen is another’s symbiotic partner, according to new biochemistry research studying the relationships between ticks and bacteria, like the one that causes Lyme disease and others found on ticks’ prey.

“Borrelia is a symbiote for the tick — it doesn’t cause any harm and maybe benefits the tick in some ways. And the skin bacteria on the host, like on humans or mice, is a symbiote for them,” said lead author Beth Hayes, a biochemist studying vector pathogens at the University of California, San Francisco. “But if you swap that, staph on the skin is a pathogen for the tick and Borrelia is a pathogen for the human. It’s this clash of symbiote versus pathogen: in what context is it a symbiote or a pathogen?”

Hayes is a staff scientist and lab manager in Seemay Chou’s lab at UCSF. Chou, Hayes and their colleagues conduct much research on microbes and ticks, previously finding that ticks are able to spread Lyme and other diseases so well because, millions of years ago, they picked up a gene from bacteria that allows them to manufacture an enzyme destructive to many microbes — but not the Borrelia responsible for Lyme.

“Bacteria exchange DNA with each other all the time, but what’s remarkable is that 40 million years ago a gene in bacteria jumped across kingdoms all the way into ticks,” Chou said in a statement. “The ticks effectively stole a page out of the bacteria’s playbook, repurposing their arsenal to use against them.”

The new research, published Thursday in the journal Cell, hones in on an antibacterial enzyme in blacklegged ticks, also known as deer ticks, called domesticated amidase effector 2, or Dae2. This enzyme protects the parasitic arachnids from the germs they find on their prey.

The Dae2 enzyme lets ticks safely burrow into human skin and spread pathogens that can cause diseases including typhus, spotted fevers, tick paralysis and Lyme, a curable bacterial infection that can harm the joints, heart or nervous system if not treated.

Lyme disease is caused by bacteria in the Borrelia genus, which can be carried by ticks in the Ixodes genus, such as deer ticks. Ticks like these spread Lyme to an estimated 300,000 people in the U.S. annually, according to the Centers for Disease Control and Prevention.

Researcher Seemay Chou examines ticks in a test tube. (Credit: Lauren J. Young/NPR Science Friday.)

Hayes and her colleagues found that microbes living on the skin of ticks’ prey — for instance, the Staphylococcus epidermidis bacteria that constitutes a normal part of the human microbiome — would kill the ticks if it weren’t for their protective Dae2 enzyme. Notably, Dae2 does not destroy the Lyme-causing Borrelia in ticks.

“Dae2 and the amidase effectors in this family target the bacterial cell wall. In gram-negative bacteria, there’s an external, outer membrane that shields the environment from that cell wall,” Hayes said in an interview. “Borrelia bergdorferi also has an outer membrane, so the cell wall is protected from these amidase effectors, Dae2. While we’ve shown that, enzymatically, Dae2 can degrade the cell wall of Borrelia bergdorferi, it can’t access it because of that outer membrane. The symbiotes that are on host skin, like Staph, are gram-positives — and gram-positives don’t have that outer membrane, so their cell wall is exposed to the environment.”

But ticks depend on that Dae2 enzyme. By limiting ticks’ ability to express Dae2 — a combination of carefully microinjecting antibodies to limit the efficacy of existing Dae2 and suppressing the enzyme with RNA interference techniques — the scientists could effectively block the enzyme from working.

“We can use an antibody that neutralizes the activity of the protein, and we can down the expression of Dae2 in the tick,” Hayes said. “By doing both of those, and injecting some of these skin commensals [such as Staphylococcus epidermidis], we see that if you block Dae2 activity, the ticks die faster and the levels of bacteria expand to a higher level. So we conclude that without Dae2, these bacteria are just taking over and expanding and killing the tick.”

That is to say, the microcultures persisting on our skin would be deadly for the ticks were it not for the Dae2 shielding them from our Staph — a symbiote to us, a pathogen to Dae2-deprived ticks.

“The word ‘pathogen’ is used in our language to describe a bacteria as ‘bad’ as opposed to ‘good,’ but in reality, ‘pathogen’ is referring to a very specific context rather than an intrinsic identity,” Chou said in the statement.

Hayes is careful to emphasize that this research does not identify a silver-bullet solution to stop the spread of Lyme and the other pathogens ticks spread to humans and animals. Nor do the scientists claim that the Dae2 enzyme is the only factor that permits Borrelia to persist in ticks – there may be other co-effectors at work in the organisms’ interactions.

“If we can target other aspects of tick biology, we might be able to stop not only Lyme disease, but other vector-borne diseases,” Hayes said. “The tick that spreads Lyme disease often can spread 16 other pathogens to humans and livestock. So it’s not just about Lyme disease; Lyme disease is why people care about ticks, usually, but lots of viruses are also transmitted by ticks, some parasites are transmitted by ticks — there’s multiple ways we can go about trying to block transmission to humans, by targeting the tick.”

Hayes says her future research may explore why some ticks prefer to prey on mammals while others choose lizards, and whether these preferences between hosts prompted their own adaptations or, alternatively, whether the adaptations suggest a host preference.

“The beautiful thing about vector biology is that it’s like a huge puzzle that we’re slowly piecing together to understand how it fits into one big picture,” Chou said in the statement. “Solving this puzzle is an important step toward the longer-term goal of preventing the spread of debilitating diseases like Lyme.”

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