Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes

Abstract

In little more than 30 years, Lyme disease, which is caused by the spirochaete Borrelia burgdorferi, has risen from relative obscurity to become a global public health problem and a prototype of an emerging infection. During this period, there has been an extraordinary accumulation of knowledge on the phylogenetic diversity, molecular biology, genetics and host interactions of B. burgdorferi. In this Review, we integrate this large body of information into a cohesive picture of the molecular and cellular events that transpire as Lyme disease spirochaetes transit between their arthropod and vertebrate hosts during the enzootic cycle.

Structural insights into Helicobacter pylori oncoprotein CagA interaction with β1 integrin

“…These bacteria cause Lyme disease and use outer surface proteins to adhere to human cells once transmitted by tick bites (reviewed in ref. 32). Although an interaction of OspA with β1-integrin receptors has not been described, a direct interaction of OspA and OspB with the complement receptor 3 (CR3) has been reported (33).…”

The Fur homologue BosR requires Arg39 to activate rpoS transcription in Borrelia burgdorferi and thereby direct spirochaete infection in mice

“…Others have shown that bosR is required for B. burgdorferi to activate expression of the alternative sigma factor RpoS (Hyde et al, 2009;Ouyang et al, 2009). Because RpoS controls the expression of virulence factors needed for mammalian infection (Radolf et al, 2012), failure to upregulate rpoS could account for why the spirochaetes expressing BosRR39K were non-infectious. Assays carried out to determine the level of rpoS transcript present in the spirochaetes grown under conditions conducive to rpoS expression found that while the BosR-expressing spirochaetes did transcribe rpoS, the BosRR39K-expressing spirochaetes did not.…”

“…Furthermore, the BosR-expressing spirochaetes produced high levels of ospC transcript and OspC protein while the BosRR39K-expressing spirochaetes did not. Transcription of ospC is known to require RpoS (Radolf et al, 2012). In vivo, OspC is expressed on the surface of the spirochaete at the point when the spirochaete moves from the gut of the tick into the haemolymph just prior to invading a mammalian host (Grimm et al, 2004;Pal et al, 2004;Tilly et al, 2006).…”

“…To do this, B. burgdorferi employs a separate set of genes for each of these environments. Determining how the spirochaete turns these genes on and off is currently an area of intense research (Radolf et al, 2012;Samuels, 2011).…”

“…In B. burgdorferi, many of the genes required for mammalian infection are under the control of the alternative sigma factor RpoS (Radolf et al, 2012). Transcription of rpoS in B. burgdorferi is complex.…”