09 July 2020
Secreted protein critical to cattle diseases
Published online 11 February 2015
Genome screening identifies protein critical to a tick-borne parasite, and explains resistance to current treatment drug.
The tick-borne parasite Theileria causes major diseases in cattle throughout tropical and subtropical regions. While endemic cattle can be resistant, the more productive European breeds are especially susceptible.
In a paper appearing in Nature, a research team has revealed the molecular machinery Theileria uses to hijack bovine cells, offering hope of improved treatment1.
Theileria causes the host’s cells to multiply uncontrollably during infection. To understand how it does this, the team screened the Theileria genome to identify candidate genes encoding secreted signalling proteins.
One gene, Tapin1, emerged as a likely candidate because of its similarity to a mammalian gene which regulates cell proliferation.
The team showed that Theileria-secreted protein TaPIN1 activates an oncogenic signalling pathway in host cells. Through a series of experiments, they demonstrated that the anti-Theileria drug buparvaquone binds to TaPIN1, preventing its activity, and, with help from Moez Mhadhbi of Université de la Manouba in Tunisia, they identified the mutation preventing this interaction in emerging buparvaquone-resistant Theileria strains.
“Other known PIN1 inhibitors might still be effective against mutant buparvaquone-resistant PIN1,” says Jonathan Weitzman of the Université Paris Diderot, who led the study. In addition, variation in PIN1 might underlie the differences in sensitivity to Theileria shown by cattle breeds, although the question awaits further investigation.
Marsolier, J. et al. Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation. Nature http://dx.doi.org/10.1038/nature14044 (2015).