Ticks can have reasons to distrust us as much as we do them.
Bacteria that are potentially deadly to blood suckers live on human skin. A new study finds that a gene from bacteria that ticks into its genetic code about 40 million years ago helps protect arachnids from potential microbial killers.
That gene produces a protein, called Dae2, that black-legged ticks (Ixodes scapularis) can use to prevent microbial threats, researchers reported Dec. 10 in Cell. But it is not a weapon of equal opportunity. In a test tube, the protein does not get into bacteria that do not bother the ticks, including Borrelia burgdorferi, the bacterial cause of Lyme disease.
The finding may explain how ticks can overcome human defenses to transmit the disease through their bite, including Lyme disease, the most common tick-borne disease in North America (SN: 23/06/16).
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The saliva of arachnids harbors many proteins that kill bacteria. But few studies have looked at how these proteins allow ticks to defend themselves against certain microbes while conserving species that are not dangerous to ticks, says Albert Mulenga, a vector biologist at Texas A&M University College Station who did not participate in the study. These studies could help scientists identify proteins crucial to tick feeding and disease transmission. Researchers can then develop ways to interfere with these proteins, preventing ticks from spreading the disease.
Bacteria today use their version of Dae2 to attack and kill other nutrient-competing bacteria by targeting and degrading a cell wall component. Without that component, rival bacterial cells decompose and die. But it was not clear how black-legged ticks use their version of Dae2, which is found in the saliva and ticks of the tick.
The biggest question was what bacteria makes the Dae2 target of ticks, says Seemay Chou, a microbiologist and biochemist at the University of California, San Francisco.
Chou and colleagues predicted that Dae2 could help black-legged ticks control the growth of B. burgdorferi. Previous work has shown that ticks without Dae2 carried more of the Lyme disease microbe than ticks with Dae2 when arachnids fed on mice infected with the microbe. But repeated experiments found that the protein could not kill bacteria in a test tube, which suggested the team's hypothesis was wrong.
“We wanted it to be true so much that we lacked the red lights that told us that couldn’t be the case,” says Beth Hayes, a microbiologist at Chou’s lab.
When Chou, Hayes, and colleagues finally began testing the protein against other types of bacteria, the Dae2 in the ticks proved surprisingly effective. In a test tube, Dae2 killed Bacillus subtilis, a common bacterial species found in the soil, as well as species that live on human skin such as Staphylococcus epidermidis and Corynebacterium propinquum. These bacteria do not usually cause disease in people. But it could be bad news for ticks, the researchers concluded.
When ticks that were prevented from producing Dae2 or had their activity blocked were fed mice, arachnids tended to have higher levels of Staphylococcus bacteria than ticks with active Dae2. And when researchers infected mites that lacked Dae2 with S. epidermidis, less than 40 percent survived more than a day. However, most Dae2-infected ticks survived as long as uninfected ticks.
Looking back, “it really doesn’t make sense to look at things that survive and thrive with ticks,” Chou says. "The Lyme pathogen is clearly in a harmonious association with the tick, so if the tick's immune system has evolved to target something, it's all things that aren't."
It is still unclear what can happen to ticks found in nature by Staphylococcus bacteria. “We don’t really know how many bacteria are in the blood meal while they are feeding (ticks),” Mulenga says. Arachnids may be exposed to non-lethal levels but may have other negative effects, such as preventing ticks from progressing in their life cycle.
Still, the findings emphasize that ticks are “really blood-sucking machines” and highlight that the word “pathogen” is just a state, depending on who the host is, Chou says. As ticks feed on blood, there is a “mirror situation in which ticks carry the Lyme pathogen, which is very bad for us and the microbes in our skin are very bad for ticks,” he says.