Borrelia burgdorferi OspC Protein Required Exclusively in a Crucial Early Stage of Mammalian Infection

Abstract

This study demonstrates a strict temporal requirement for a virulence determinant of the Lyme disease spirochete Borrelia burgdorferi during a unique point in its natural infection cycle, which alternates between ticks and small mammals. OspC is a major surface protein produced by B. burgdorferi when infected ticks feed but whose synthesis decreases after transmission to a mammalian host. We have previously shown that spirochetes lacking OspC are competent to replicate in and migrate to the salivary glands of the tick vector but do not infect mice. Here we assessed the timing of the requirement for OspC by using an ospC mutant complemented with an unstable copy of the ospC gene and show that B. burgdorferi's requirement for OspC is specific to the mammal and limited to a critical early stage of mammalian infection. By using this unique system, we found that most bacterial reisolates from mice persistently infected with the initially complemented ospC mutant strain no longer carried the wild-type copy of ospC. Such spirochetes were acquired by feeding ticks and migrated to the tick salivary glands during subsequent feeding. Despite normal behavior in ticks, these ospC mutant spirochetes did not infect naive mice. ospC mutant spirochetes from persistently infected mice also failed to infect naive mice by tissue transplantation. We conclude that OspC is indispensable for establishing infection by B. burgdorferi in mammals but is not required at any other point of the mouse-tick infection cycle.

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

“…While specific molecular functions of OspC are not yet clear, it is known that ospC is required for host infection and is among the most differentially expressed genes during host invasion (Brooks et al 2003;Grimm et al 2004;Liang et al 2004;Tilly et al 2006;Antonara et al 2010). Considering that ospC is a serotype determinant of B. burgdorferi s.l., negative FDS operating at ospC is highly plausible.…”

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

“…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). Therefore, although genes other than rpoS may have had a role in making the BosRR39K-expressing spirochaetes non-infectious, failure to upregulate rpoS appears to have been a major cause.…”

Biology of Infection with Borrelia burgdorferi

“…Some are involved in early infection, such as OspC [112][113][114][115][116], which are presumably required for host colonization or resistance to innate immunity. Others are involved in resistance to acquired immunity, such as VlsE [13,109,117,118].…”

“…The OspC product has been shown to be required for an early stage of mammalian infection [113][114][115][116] and conflicting data have been presented regarding its importance in tick transmission [113,114,119,120]. OspC production begins in feeding ticks (or immediately after needle inoculation, Fig.…”

“…1) and lasts for the first couple of weeks of mammalian infection [49,51,103,[121][122][123]. Once the bacteria are established in a host, OspC production is not required for persistence [114]. The molecular function of the OspC protein is undefined, although the crystal structure of the protein predicts that it binds a small ligand [124,125].…”