Fig. 2. Acquisition of Borrelia burgdorferi.

a | When feeding on an infected host, the Ixodes scapularis tick takes up Borrelia burgdorferi with the bloodmeal. The tick injects the salivary protein SALP25D into the host skin to dampen inflammation at the feeding site. SALP25D quenches reactive oxygen species generated by activated neutrophils at the bite site¹⁸⁶. The activity of SALP25D enhances B. burgdorferi acquisition by the tick, possibly by increasing viability of the spirochaetes at the bite site. SALP12 functions as a chemoattractant for B. burgdorferi and increases the quantity of spirochetes entering the tick³⁶. Entry of B. burgdorferi into the tick induces upregulation of Hk1–Rrp1 and downregulation of RpoS, resulting in production of c-di-GMP, an important molecule regulating expression of outer surface proteins. b | Spirochaetes ingested in the bloodmeal adhere to the tick gut and remain in this organ until a subsequent tick feeding. B. burgdorferi expresses the outer surface proteins OspA and OspB, which protect spirochaetes from harmful components in host blood⁵⁶, including antibodies and complement, and enable them to adhere to and persist in the gut^44,45,47. OspA interacts specifically with the tick receptor TROSPA, which is located on the luminal surface of gut epithelial cells and is upregulated when spirochaetes are ingested⁴⁸. tHRF, tick histamine release factor.