Lyme disease and relapsing fever spirochetes

Borrelia burgdorferi sensu lato causes Lyme borreliosis in a variety of animals and humans. These atypical bacterial pathogens are maintained in a complex enzootic life cycle that primarily involves a vertebrate host and Ixodes spp. ticks. In the Northeastern United States, I. scapularis is the main vector, while wild rodents serve as the mammalian reservoir host. As B. burgdorferi is transmitted only by I. scapularis and closely related ticks, the spirochete-tick interactions are thought to be highly specific. Various borrelial and arthropod proteins that directly or indirectly contribute to the natural cycle of B. burgdorferi infection have been identified. Discrete molecular interactions between spirochetes and tick components also have been discovered, which often play critical roles in pathogen persistence and transmission by the arthropod vector. This chapter will focus on the past discoveries and future challenges that are relevant to our understanding of the molecular interactions between B. burgdorferi and Ixodes ticks. This information will not only impact scientific advancements in the research of ticktransmitted infections but will also contribute to the development of novel preventive measures that interfere with the B. burgdorferi life cycle. Introduction Ixodes ticks transmit a wide range of infections, including Lyme disease, to animals and humans (Nadelman and Wormser, 1998; Radolf et al., 2012; Nelder et al., 2016; Steere et al., 2016; Stanek and Strle, 2018). Lyme disease is a prominent tick-borne illness (Benach et al., 1983) that features widespread distribution (Mead, 2015) and is caused by a group of spirochetes belonging to the Borrelia burgdorferi sensu lato complex (Burgdorfer et al., 1988). Recently, more virulent (albeit less prevalent) strains of Borrelia pathogens have been identified, including new clinical isolates of B. burgdorferi sensu lato, B. bissettii, B. mayonii, and B. miyamotoi, which are also transmitted by Ixodes ticks and are associated with severe human diseases (see chapter 24) (Krause et al., 2015; Pritt et al., 2016; Rudenko et al., 2016). Globally, the Borrelia species that are commonly associated with Lyme disease include B. burgdorferi sensu stricto, which is prevalent throughout the United States and Europe, and B. afzelii and B. garinii, which are distributed throughout Eurasia (Nadelman and Wormser, 1998; Piesman and Gern, 2004; Mead, 2015). In North America and Europe, Lyme disease spirochetes typically are maintained in nature through a complex tick-rodent infection cycle. Larval ticks acquire the pathogen while feeding on infected wild hosts, such as white-footed mice (Anderson et al., 1987; Anderson, 1989), and then transstadially maintain B. burgdorferi before transmitting the pathogen back to a naïve host during the subsequent blood meal (Steere, 2001; Steere et al., 2004). Humans and domesticated animals that develop Lyme disease are incidental hosts and do not play a role in the natural transmission cycle (Radolf et al., 2012). B. burgdorferi does not readily infect most tick species, suggesting that its interactions with I.