Coordinated Expression ofBorrelia burgdorferiComplement Regulator-Acquiring Surface Proteins during the Lyme Disease Spirochete's Mammal-Tick Infection Cycle

Abstract

The Lyme disease spirochete, Borrelia burgdorferi, is largely resistant to being killed by its hosts' alternative complement activation pathway. One possible resistance mechanism of these bacteria is to coat their surfaces with host complement regulators, such as factor H. Five different B. burgdorferi outer surface proteins having affinities for factor H have been identified: complement regulator-acquiring surface protein 1 (BbCRASP-1), encoded by cspA; BbCRASP-2, encoded by cspZ; and three closely related proteins, BbCRASP-3, -4, and -5, encoded by erpP, erpC, and erpA, respectively. We now present analyses of the recently identified BbCRASP-2 and cspZ expression patterns throughout the B. burgdorferi infectious cycle, plus novel analyses of BbCRASP-1 and erp-encoded BbCRASPs. Our results, combined with data from earlier studies, indicate that BbCRASP-2 is produced primarily during established mammalian infection, while BbCRASP-1 is produced during tickto-mammal and mammal-to-tick transmission stages but not during established mammalian infection, and Erp-BbCRASPs are produced from the time of transmission from infected ticks into mammals until they are later acquired by other feeding ticks. Transcription of cspZ and synthesis of BbCRASP-2 were severely repressed during cultivation in laboratory medium relative to mRNA levels observed during mammalian infection, and cspZ expression was influenced by culture temperature and pH, observations which will assist identification of the mechanisms employed by B. burgdorferi to control expression of this borrelial infectionassociated protein.

Borrelia burgdorferi bba74Is Expressed Exclusively during Tick Feeding and Is Regulated by Both Arthropod- and Mammalian Host-Specific Signals

“…RpoS also is required for the downregulation of 33 70 -dependent genes in response to mammalian host signals, among which are the tick-phase genes ospA, bba62, and lp6.6 (17,19). Relief from RpoS-mediated repression occurs almost immediately following acquisition of spirochetes by feeding naïve larvae (16,19,35,76), thereby giving rise to a period within the enzootic cycle that we have designated as the RpoS-OFF state (Fig. 5).…”

Borrelia burgdorferi complement regulator-acquiring surface proteins (BbCRASPs): Expression patterns during the mammal–tick infection cycle

“…In contrast, cspA transcripts become undetectable within two weeks of establishing mammalian infection Lederer et al, 2005;McDowell et al, 2006;Bykowski et al, 2007). Humans and laboratory mice produce limited antibody responses to BbCRASP-1, consistent with brief exposure of that protein to host immune systems .…”

“…Bacteria colonizing the midguts of unfed nymphs generally do not produce detectable levels of BbCRASPs von Lackum et al, 2005;Bykowski et al, 2007) (Fig. 2).…”

“…Erp proteins are produced by essentially all recently-acquired borreliae in the feeding larval midgut. Following completion of larval feeding and detachment from the host, B. burgdorferi reduces levels of all BbCRASPs von Lackum et al, 2005;Bykowski et al, 2007) …”

BBA70 of Borrelia burgdorferi Is a Novel Plasminogen-binding Protein

“…Mice Infections-Four Bl/6 mice (Jackson Laboratories) were infected, under laboratory conditions, by vector tick bite (Ixodes scapularis), as described previously (46). Prior to tick feeding, a sample of 10 ticks was tested to ensure they were harboring B. burgdorferi (47).…”