Borrelia burgdorferi surface protein Lmp1 facilitates pathogen dissemination through ticks as studied by an artificial membrane feeding system

Abstract

In its natural infection cycle, the pathogen of Lyme borreliosis transits between a tick vector and a mammalian host. As relatively a minor fraction of spirochetes transits between the host and the vector precluding their reliable detection at early infection, artificial membrane feeders emerged as useful tools to study roles of spirochete proteins in pathogen entry, persistence, and exit through ticks. Here we report the development of a modified membrane feeder to study the role of a Borrelia burgdorferi surface protein called Lmp1 in spirochete transitions between the murine host and ticks. We show that our membrane feeder supports the blood meal engorgement process where ticks can acquire spirochetes from the feeder containing extremely low levels of pathogens (102 cells/ml of blood). Our data revealed that in comparison to wild-type spirochetes, lmp1 deletion mutants are significantly impaired for acquisition in naïve ticks as well as transmission from infected ticks. Taking together, our data suggest that Lmp1 plays an essential role in spirochete transitions between hosts and the vector. These studies also underscore the usefulness of artificial membrane feeding system as a valuable tool to study the role of B. burgdorferi gene-products in pathogen persistence in and passage through vector ticks.

Sharing the Ride: Ixodes scapularis Symbionts and Their Interactions

“…Such membrane feeding systems have been useful for introducing specific pathogens into I. scapularis and to test different acaricides effectiveness on I. ricinus (Krober and Guerin, 2007;Oliver et al, 2016). Several recent studies have used these systems to elucidate the contribution of B. burgdorferi proteins in acquisition and transmission of mutant strains and to assess nutritional requirements for tick reproduction (Perner et al, 2016;Bernard et al, 2018;Hart et al, 2018;Koci et al, 2018). Larval ticks, though, did not successfully feed with this technique, likely due to the inability of the smaller mouthparts of larvae to penetrate through the thickness of the silicone membrane (Oliver et al, 2016).…”

Borrelia bavariensis: Vector Switch, Niche Invasion, and Geographical Spread of a Tick-Borne Bacterial Parasite

“…Some molecules that have been shown to have a function within the tick vector include the Outer surface protein A (OspA) which binds to the vector midgut molecule TROSPA (Pal et al, 2004); BBE31 which binds to the vector molecule Tre31, a protein secreted by tick midgut epithelial cells (Zhang et al, 2011); PdeB, a phosphodiesterase required for survival in, and transmission by, ticks; Lpm1, a surface molecule, depletion of which inhibits Borrelia in the vector (Koci et al, 2018); BB0365, BB0690, BptA, lp6.6, BBk32 are all required for persistence in the tick, while antigen P35 (BBA64) may play a role in tick-tohost transmission (Fikrig et al, 2000;Radolf et al, 2012;Brandt et al, 2014). In a recent study using transposon-based gene interruption approach, >100 genes were shown to be involved in Borrelia survival in larval ticks (Phelan et al, 2019).…”

Membrane directed expression in Escherichia coli of BBA57 and other virulence factors from the Lyme disease agent Borrelia burgdorferi

“…Several membrane-translocated proteins are important for Bb transmission and persistence. In ticks, OspA is essential for colonization and survival 9 and Lmp1 facilitates dissemination 10 . BB0405 is necessary for transmission from tick to mouse and for establishing infection in mice 11 .…”