B. burgdorferi is maintained in nature in an enzootic infectious cycle involving vertebrate hosts and hard ticks of the genus Ixodes (reviewed in Radolf et al. 2012). Uninfected larvae hatch from eggs and acquire B. burgdorferi by feeding on an infected animal, usually a small mammal or bird. After feeding, the larva drops to the ground and molts into the next life stage called a nymph. Nymphs feed on a second host, again usually a small mammal or bird, thus transmitting B. burgdorferi from the tick to a new reservoir. In this way, the bacterium is maintained in the environment. Occasionally, a nymph will feed on an incidental host, such as a human or dog. Humans are at most risk of being bitten during the late spring and summer, when nymphs are active. Replete nymphs drop to the ground and molt into the adult life stage. Adult ticks feed on larger animals, such as deer. After feeding, a mated adult female will lay eggs and die, and the cycle continues.
Remarkably, B. burgdorferi survives inside the tick midgut throughout the molts, when massive tissue reorganization occurs. As a result of this complex life cycle, B. burgdorferi adapts to wildly different environments (cold-blooded arthropod vector and warm-blooded vertebrate host) through its ability to persist, evade immune responses, disseminate, and spread to new hosts.