Bloodsucking ticks rely on an antibacterial enzyme stolen from ancient bacteria to survive on the human body, according to a new study, which emphasizes the findings’ potential to help slow the spread of Lyme disease.
The research, published this month in Cell, builds on previous work looking into the origins and use of the bacteria enzyme.
Ticks create an enzyme called Dae2 using a gene it gained about 40 million years ago, when it acquired the piece of genetic code from bacteria and incorporated it into its own DNA, according to 2015 research from the University of Washington.
Dae2, which is in the tick’s saliva, helps explain how the parasitic arthropod can safely sustain its bite on a host for several days. The researchers found that Dae2 kills many bacteria that live on the human skin, protecting the tick — although it had little effect on Borrelia burgdorferi, which causes Lyme disease.
While trans-kingdom DNA transfers are not uncommon, the fact that the gene is functional within ticks and didn’t become junk DNA is “more surprising” and gives hints to their evolutionary development, said Beth Hayes, a lead author of the study.
“Because the tick itself started making this protein and adopting it to the tick lifestyle, especially because it happened around the time that blood-feeding started to occur, (it) was very striking,” said Hayes, an associate specialist in biochemistry and biophysics at the University of California, San Francisco. “We think that this protein, along with others that we haven't identified, helps to evolve the blood feeding biology.”
When the scientists disrupted the gene that encodes Dae2, ticks exposed to human-skin bacteria had more on their bodies and died more quickly, implying that the skin microbiome is deadly to the parasites without the protection of the antibacterial enzyme. The Dae2-inhibited ticks also fed more slowly, leading to longer bites and smaller bodies.
The new paper came from the lab of Seemay Chou, a USCF professor and the lead author of the 2015 research that identified the origins of Dae2.
Ticks pass numerous diseases onto humans through bites, including Lyme disease, a bacterial infection with about 300,000 new U.S. cases each year that causes rashes and chronic symptoms such as fatigue and joint pain. Available treatments are imperfect, and no vaccines for Lyme disease are currently on the market, although one was withdrawn in 2002 following unfounded concerns that it caused autoimmune issues.
By considering not only the disease-causing bacteria but also the tick, human body and other parts of infection, a better solution may be discovered, said Atanas Radkov, a postdoctoral scholar in biochemistry and biophysics at UCSF and the study’s other lead author.
“There are other creative approaches if we shift our focus from the disease to actual biology, to the basic science,” Radkov said. “I think that's what we did here with this paper, which sort of changed the narrative.”
The lead authors expressed interest in finding other molecules that help ticks feed and why different breeds of ticks carry different disease-causing bacteria, which could inform how to prevent ticks from carrying Borrelia burgdorferi and other pathogens in the first place.
Hayes compared their work with efforts to prevent disease-carrying mosquitoes from biting humans — whether with nets or genetic engineering — but noted that ticks have been the subject of much less research.
“Really understanding the tick biology and what makes the tick ‘tick’ is how we're going to address and interfere with transmission,” Hayes said.
The article, “Ticks Resist Skin Commensals with Immune Factor of Bacterial Origin” was published Dec. 10 in Cell.
The authors of the study were Beth Hayes, Atanas Radkov, Fauna Yarza, Sebastian Flores, Jungyun Kim, Ziyi Zhao, Victoria Bowcut and Seemay Chou, University of California, San Francisco; Liron Marnin and Joao Pedra, University of Maryland; Jacob Biboy and Waldemar Vollmer, Newcastle University; Katrina Lexa, Denali Therapeutics. The lead authors were Beth Hayes and Atanas Radkov.