Written by Dr Lee Haines, researcher at the Liverpool School of Tropical Medicine, UK

Imagine you risked dying of a bacterial infection every time you needed to eat.  If you were a tick, you would be in trouble because feeding takes a long time – between 3-7 days. What would you do to make eating safer?A research team at the University of California San Francisco is trying to find it out. The team had previously found that the blacklegged tick, Ixodes scapularis, overcame the problem by borrowing a bacterial toxin gene to kill other bacteria1

This gene, named domesticated amidase effector 2 (dae2), encodes a potent antibacterial enzyme that degrades the bacterial cell wall. Given that ticks inevitably encounter bacteria naturally colonising mammalian skin, the authors reasoned these bacteria could cause harm by either directly infecting the tick or the bite site during prolonged feeding. Thus it would be advantageous for the tick to produce antimicrobial substances during feeding to prevent harmful bacterial infections. The authors proposed that Dae2 was secreted in tick saliva to allow the enzyme to directly kill skin-associated bacteria.  

To test this hypothesis, the team first created 3D models of Dae2 to compare its shape to its bacterial ancestor protein (Tae2)2. Using computer programs to simulate how Dae2 would bind to the bacterial cell wall, coupled to lab tests with bacteria isolated from ticks and mammalian skin, the authors determined synthetic Dae2 could kill a much wider range of bacteria compared to the ancestral enzyme Tae2.  This exciting discovery led the team to screen Dae2 activity against other skin microbes found at the tick-host interface during feeding. They showed Dae2 has a broad activity against several species of skin-associated bacteria.

But where does this microbial killing happen – in the tick gut after bloodmeal ingestion or during biting and salivation?  Dae2 is made in response to feeding in both the adult and nymphal tick stages, and it is secreted into tick saliva.  Using elegant techniques to block Dae2 activity in the tick, the authors showed how important this protein is for tick feeding and protection from bacterial infection.  Ticks with biochemically reduced levels of Dae2 enzyme ingested significantly smaller blood meals and suffered from elevated bacterial infections, which led to higher death rates compared to control ticks having normal levels of Dae22.  

Together, these observations support the claim that the Dae2 enzyme was adapted by ticks to protect them from a wide selection of dangerous, skin-associated bacteria encountered during continuous and prolonged blood feeding. The black-legged tick is also a vector of Borrelia burgdorferi, the bacterium causing Lyme disease. Future research may help understand better how the bacterial toxin gene was acquired by the tick, and how it could be used to control Lyme disease or other tick-borne pathogens.

Read the italian version here.

References

[1] Chou S, Daugherty MD, Peterson SB, et al. 2015. Transferred interbacterial antagonism genes augment eukaryotic innate immune function. Nature 518(7537): 98‐101. doi: 10.1038/nature13965

[2] Hayes BM, Radkov AD, Yarza F, et al. 2020. Immune factor of bacterial origin protects ticks against host microbial commensals. bioRxiv April 11. doi: 10.1101/2020.04.10.036376