Interactions between Borrelia burgdorferi and its hosts across the enzootic cycle

Abstract

Arthropod-borne diseases are becoming increasingly prevalent across the globe, and an understanding of the pathogen-arthropod interface can be an important tool in control of these diseases.Ixodes ticks carry many pathogens of human importance, including Anaplasma, Babesia, Borrelia, tick-borne encephalitis virus and Powassan virus. The most researched of these pathogens is the spirochete Borrelia burgdorferi, the causative agent of Lyme disease and the most common vector-borne disease in the United States. [1][2][3] There are three important components to maintenance of the B. burgdorferi life cycle: the spirochete, the invertebrate tick vector and the vertebrate host (Figure 1).Ixodes ticks are haematophagous and take one blood meal during the larval, nymph and adult stage of their lifecycle. B. burgdorferi is not transmitted from adult ticks to eggs, so larval ticks must acquire the spirochetes from infected animals, such as birds and mice, with the first blood meal. The spirochetes will remain within the tick after feeding and moulting into the nymphal stage. A B. burgdorferi infected nymph will feed on another reservoir host and transmit the spirochetes, continuing the enzootic cycle. After another moult into the adult stage, the adult tick will typically feed on larger animals (such as deer) that may not be competent reservoir hosts for B. burgdorferi but are critical to tick mating. Ticks in the nymphal stage are primarily responsible for transmission of B. burgdorferi to humans, but humans are not important in the enzootic cycle and are considered dead-end hosts. 1The tick salivary glands and midgut play important roles in the colonization and transmission of B. burgdorferi. During acquisition from an infected host that occurs with the tick blood meal, B. burgdorferi enters the tick with blood and interacts with tick

High-resolution crystal structure of theBorreliella burgdorferiPlzA protein in complex with c-di-GMP: new insights into the interaction of c-di-GMP with the novel xPilZ domain

“…The LD spirochetes persist in nature in an enzootic cycle involving Ixodes ticks and a diverse and expanding array of mammals and birds (Helble, McCarthy and Hu 2020 ). The LD spirochetes must be able to adapt to highly variable environmental conditions encountered during the enzootic cycle.…”

The Infectivity Gene bbk13 Is Important for Multiple Phases of the Borrelia burgdorferi Enzootic Cycle

“…Consistent with previous findings for B. burgdorferi lacking the entire linear plasmid 36 (lp36) ( 27 ), on which the bbk13 gene resides ( 28 ), no bbk13 -dependent defect in B. burgdorferi replication or survival was detected across the tick life stages. Tick bite transmission of B. burgdorferi induces significant changes in both the spirochete and the mammalian host to promote infection ( 8 , 9 ), which are not recapitulated by in vitro -grown B. burgdorferi delivered by needle inoculation. Therefore, we sought to assess the contribution of the bbk13 gene to mouse infection by tick bite transmission.…”

“…However, needle inoculation is an artificial route of infection that excludes the contribution of the tick vector to B. burgdorferi transmission—both its influence on B. burgdorferi itself and its influence on the host microenvironment at the site of feeding. B. burgdorferi adapts to the conditions present in the unfed tick and undergoes significant transcriptional changes during tick feeding, potentiating its infectivity ( 8 , 9 ). Moreover, the feeding activity of the ticks themselves, particularly the influence of the tick saliva on the skin feeding site, affects B. burgdorferi infection ( 10 – 12 ).…”

BB0761, a MepM homolog, contributes to Borrelia burgdorferi cell division and mammalian infectivity

“…During its cycle between tick and mammalian hosts, B. burgdorferi encounters many stressful conditions. It is critical for B. burgdorferi to cope with environmental stresses such as osmotic pressure and oxidative stress in order to survive in these two drastically disparate conditions (Curtis et al, 2018;Gherardini, 2013;Helble et al, 2021;Kurokawa et al, 2020;Pal et al, 2021;…”

“…It is now well‐established that the RpoN‐RpoS regulatory pathway is central to B. burgdorferi environmental adaptation. More specifically, this pathway activates the expression of many mammalian‐infection associated virulence determinants, and simultaneously represses the expression of many factors required for tick colonization, survival, and/or persistence (Blevins et al, 2009; Caimano et al, 2005; Caimano et al, 2019; Grove et al, 2017; Helble et al, 2021; Hubner et al, 2001; Kurokawa et al, 2020; Ouyang et al, 2008; Ouyang et al, 2012; Radolf et al, 2012; Samuels, 2011; Samuels et al, 2021; Yang et al, 2003; Ye, Zhou, et al, 2016). With recent advances in our understanding of borrelial genetics, additional virulence mechanisms have been identified in B. burgdorferi .…”