Outer surface protein polymorphisms linked to host‐spirochete association in Lyme borreliae

Abstract

Summary Lyme borreliosis is caused by multiple species of the spirochete bacteria Borrelia burgdorferi sensu lato. The spirochetes are transmitted by ticks to vertebrate hosts including small and mediumsized mammals, birds, reptiles, and humans. Strain-to-strain variation in host specific infectivity has been documented, but the molecular basis that drives this differentiation is still unclear. Spirochetes possess the ability to evade host immune responses and colonize host tissues to establish infection in vertebrate hosts. In turn, hosts have developed distinct levels of immune responses when invaded by different species/strains of Lyme borreliae. Similarly, the ability of Lyme borreliae to colonize host tissues varies among different spirochete species/strains. One potential mechanism that drives this strain-to-strain variation of immune evasion and colonization is the polymorphic outer surface proteins produced by Lyme borreliae. In this review, we summarize research on strain-to-strain variation in host competence and discuss the evidence that supports the role of spirocheteproduced protein polymorphisms in driving this variation in host specialization. Such information will provide greater insights into the adaptive mechanisms driving host and Lyme borreliae association, which will lead to the development of interventions to block pathogen spread and eventually reduce Lyme borreliosis health burden.

New Insights Into CRASP-Mediated Complement Evasion in the Lyme Disease Enzootic Cycle

“…These findings imply an allelic variation of CspA-mediated FH-binding activity. Such results also lead to an intriguing possibility that CspA determines spirochete host tropism by driving the transmission from ticks to specific hosts (Kurtenbach et al, 2002;Kraiczy, 2016;Tufts et al, 2019).…”

“…Among the ∼20 Borrelia species that comprise the sensu lato complex, at least six have been confirmed to cause LD in humans including Borrelia (B.) burgdorferi sensu stricto (hereafter referred as B. burgdorferi), B. afzelii, B. garinii, B. spielmanii, B. bavariensis, and B. mayonii, all of which are transmitted by Ixodes ticks and maintained in diverse reservoir hosts (mainly small mammals and birds) (Tufts et al, 2019). Upon tick feeding, spirochetes are exposed to host blood and the first line of innate immunity which they must overcome to survive (Hovius et al, 2007;Steere et al, 2016; Figure 1).…”

The need to unravel the twisted nature of the Borrelia burgdorferi sensu lato complex across Europe

“…It is suggested that it diverged at some point from B. garinii, which is known to be bird-specific in terms of reservoir hosts and made a switch that enabled B. bavarensis to be associated with small mammals [5]. Genetic analysis is a valuable tool that has been employed extensively to determine important factors responsible for the pathogenesis of many bacterial species and could certainly answer questions regarding how genetic composition, including the identified CRASP genes, could lead to differences in reservoir host association [81,88]. Advances in genetic manipulation [89] and the release of the complete genome of B. burgdorferi ss [2] has allowed investigators to identify the role of individual genes in the context of experimental Lyme borreliosis.…”

“…The molecular mechanisms behind the difference in tissue tropism are not fully clear so far, but decorin-binding proteins may well play a significant role in varying tissue tropisms associated with different Borrelia genospecies. The association of B. burgdorferi genospecies with vertebrate reservoir host species appears to be strongly affected by the polymorphism of borrelial proteins [81,82]. The complement sensitivity or resistance of Borrelia genospecies is one of the crucial components governing the Borrelia-host relationship.…”

“…The complement system is one of the major innate defence mechanisms B. burgdorferi has to overcome to establish a stable infection of the mammalian host. Different genospecies of B. burgdorferi differ in their sensitivity to human and animal sera [81,83]. A number of borrelial polymorphic proteins may be involved in host-to-host differences in complement evasion.…”