Bacteria hijack tick cell defenses to spread disease

(Press-News.org) PULLMAN, Wash. – Washington State University researchers have discovered how the bacteria that cause anaplasmosis and Lyme disease hijack cellular processes in ticks to ensure their survival and spread to new hosts, including humans.

Based in the College of Veterinary Medicine, the team found that the bacteria can manipulate a protein known as ATF6, which helps cells detect and respond to infection, to support its own growth and survival inside the tick. The findings, published in the journal Proceedings of the National Academy of Sciences, could serve as a launching point for developing methods to eliminate the bacteria in ticks before they are transmitted to humans and other animals.

“Most research has looked at how these bacteria interact with humans and animals and not how they survive and spread in ticks,” said Kaylee Vosbigian, a doctoral student and lead author on the study. “What we have found could open the door to targeting these pathogens in ticks, before they are ever a threat to people.”

Vosbigian and her advisor, Dana Shaw, the corresponding author of the study and an associate professor in the Department of Veterinary Microbiology and Pathology, focused their research on Ixodes scapularis, also known as the blacklegged tick, which is responsible for spreading both Anaplasma phagocytophilum and Borrelia burgdorferi, the causative agents of anaplasmosis and Lyme disease. Both diseases are becoming increasingly common and can cause serious illness in humans and animals.

The team discovered that when ATF6 is activated in tick cells, it triggers the production of stomatin, a protein that helps move cholesterol through cells as part of a normal cellular processes. The bacteria exploit this process against their tick hosts, using the cholesterol –which they need to grow and build their own cell membranes but cannot produce themselves – to support their own survival and success.

“Stomatin plays a variety of roles in the cell, but one of its key functions is helping shuttle cholesterol to different areas,” Vosbigian said. “The bacteria take advantage of this, essentially stealing the cholesterol they need to survive.”

When the researchers blocked the production of stomatin, restricting the availability of cholesterol, bacterial growth is significantly reduced. The researchers believe this shows targeting the ATF6-stomatin pathway could lead to new methods for interrupting the disease cycle in ticks before transmission occurs.

As part of the study, Vosbigian also developed a new research tool called ArthroQuest, a free, web-based platform hosted by WSU that allows scientists to search the genomes of ticks, mosquitoes, lice, sand flies, mites, fleas and other arthropod vectors for transcription factor binding sites – genetic switches like ATF6 that control gene activity.

“There aren’t many tools out there for studying gene regulation in arthropods,” Vosbigian said. “Most are built for humans or model species like fruit flies, which are genetically very different from ticks.”

Using ArthroQuest, the team found that ATF6-regulated control of stomatin appears to be prevalent in blood-feeding arthropods. Since the hijacking of cholesterol and other lipids is common among arthropod-borne pathogens, the researchers suspect many may also exploit ATF6.

“We know many other vector-borne pathogens, like Borrelia burgdorferi and the malaria-causing parasite Plasmodium, rely on cholesterol and other lipids from their hosts,” Shaw said. “So, the fact that this ATF6-stomatin pathway exists in other arthropods could be relevant to a wide range of disease systems.”

The research was supported in part by a National Institutes of Health R01 grant and a College of Veterinary Medicine intramural seed grant.

END