ABOVE: An adult female Asian longhorned tick (Haemaphysalis longicornis)

Many species of ticks need blood meals to grow, develop, and reproduce. During those blood meals, they can transmit diseases to their hosts. Researchers have known for several years that treating ticks with antibiotics to do away with bacteria that live inside them affects blood intake, but it wasn’t clear why. Now, a study published September 14 in Cell Host & Microbe shows that one such bacterial symbiont, Coxiella, influences blood feeding by the Asian longhorned tick (Haemaphysalis longicornis) by contributing to tick tryptophan metabolism, thus regulating serotonin production.

“That microbes . . . influence brain and behavior is really fascinating,” says Carlos Ribeiro, a neuroscientist at Champalimaud Centre for the Unknown in Portugal who did not participate in the study. “We are moving away from the phase where we are just documenting these effects [to] starting to understand mechanisms and how those affect, in a meaningful way, phenotypes,” he adds. He also credits the authors for using a nonmodel organism for their study: “to dissect mechanisms in such a system is not trivial.”

Biologist Jingwen Wang and their team at Fudan University in China initially set out to understand the effects of symbionts on the capacity of ticks to transmit pathogens. The researchers shifted their focus when they treated the ticks with antibiotics to reduce the population of their primary symbiont, Coxiella, and found that the majority of ticks stopped eating. “Since blood feeding makes ticks the competent disease transmitting vector, we changed our interest to understand the influence of symbiont on the regulation of tick appetite,” Wang writes in an email to The Scientist. 

The team compared gene expression in untreated ticks and those treated with tetracycline, which depletes Coxiella, and found that loss of the symbiont changes the activity of genes involved in amino acid metabolism. They also determined that the Coxiella genome encodes the proteins needed for a pathway that is not found in animals and results in the production of the molecule chorismate, which can then be used to generate aromatic amino acids, such as tryptophan.

The researchers hypothesized that disruptions to tryptophan synthesis might also affect the hormone serotonin (also known as 5-HT), which is made from tryptophan, and indeed found that ticks treated with tetracycline had lower levels of serotonin. They also showed that disrupting serotonin production and signaling in ticks with normal symbiont populations caused a dip in blood intake. Conversely, tetracycline-treated ticks supplemented with chorismate, tryptophan, or serotonin fed normally again.

That microbes . . . influence brain and behavior is really fascinating.

—Carlos Ribeiro, Champalimaud Centre for the Unknown

Coxiella mainly resides in the ticks’ excretory organs and ovaries, but the team found that antibiotic treatment didn’t influence serotonin levels in those tissues. Instead, the drug reduced serotonin levels in the tick midgut and synganglion, a bundle of nerves found near the esophagus. The researchers determined that the symbiont regulates serotonin biosynthesis remotely by secreting chorismate into the tick circulatory system.

From previous work, “we know that symbionts are important during high metabolic activity, which includes feeding and egg production,” says Yuval Gottlieb-Dror, an entomologist at the Hebrew University of Jerusalem who did not participate in the new study. “From the paper we understand part of the mechanism: the symbiont is producing a metabolite that affects the biosynthesis of host 5-HT,” she adds, “but we don't know the exact process.”

“Serotonin is actually produced by the tick, not just through the symbionts, because when the symbiont is eliminated, you still see 5-HT,” just at lower levels, Gottlieb-Dror adds, “so the question is, what is the actual mechanism that makes the symbiont necessary?” Plus, some tick species don’t have a specific symbiont, she adds, “so how are they managing to overcome this symbiont precursor production of serotonin and therefore feed on blood?”

Another open question, according to evolutionary biologist Rahul Raghavan of the University of Texas at San Antonio who was not involved in the work, is, “if the bacteria is affecting the amount of blood being taken in by the tick, how is that affecting the tick’s fitness and its ability to reproduce [and], from a pathogenicity point of view, how is that affecting bacterial transmission?”

Prior work has shown that if a symbiotic bacterium provides some kind of function that is critical to the host insect, the bacterium is then maintained in a dedicated cell type or tissue. “The host makes sure that the bacterium is not lost because if it’s lost, then the host cannot survive,” Raghavan says, “but ticks seem to lack similar structures.” And compared to insects that typically form long-term relationships with beneficial endosymbionts, most tick-endosymbiont relationships appear to be short-lived in terms of evolutionary time, he adds. “The question is, if it is so important for their blood feeding, then why is . . . Coxiella not permanently associated with ticks?”