Borrelia burgdorferi complement regulator-acquiring surface protein 2 does not contribute to complement resistance or host infectivity.
Borrelia burgdorferi, the pathogen of Lyme disease, cycles in nature through Ixodes ticks and mammalian hosts. At least five Complement Regulator-Acquiring Surface Proteins (BbCRASPs) are produced by B. burgdorferi, which are thought to assist spirochetes in host immune evasion. Recent studies established that BbCRASP-2 is preferentially expressed in mammals, and elicits robust antibody response in infected hosts, including humans. We show that BbCRASP-2 is ubiquitously expressed in diverse murine tissues, but not in ticks, reinforcing a role of BbCRASP-2 in conferring B. burgdorferi defense against persistent host immune threats, such as complement. BbCRASP-2 immunization, however, fails to protect mice from B. burgdorferi infection and does not modify disease, as reflected by the development of arthritis. An infectious BbCRASP-2 mutant was generated, therefore, to examine the precise role of the gene product in spirochete infectivity. Similar to wild type B. burgdorferi, BbCRASP-2 mutants remain insensitive to complement-mediated killing in vitro, retain full murine infectivity and induce arthritis. Quantitative RT-PCR assessment indicates that survivability of BbCRASP-2-deficient B. burgdorferi is not due to altered expression of other BbCRASPs. Together, these results suggest that the function of a selectively expressed B. burgdorferi gene, BbCRASP-2, is not essential for complement resistance or infectivity in the murine host.
Coleman
Adam S
AS
Department of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America.
Yang
Xiuli
X
Kumar
Manish
M
Zhang
Xinyue
X
Promnares
Kamoltip
K
Shroder
Deborah
D
Kenedy
Melisha R
MR
Anderson
John F
JF
Akins
Darrin R
DR
Pal
Utpal
U
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D003165:Complement System Proteins / Q000502:physiology; D019286:Endopeptidase K / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008193:Lyme Disease / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice / Q000382:microbiology; D008809:Mice, Inbred C3H; D009154:Mutation; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis; D013987:Ticks / Q000382:microbiology
D001426:Bacterial Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C440651:complement regulator-acquiring surface proteins, Borrelia burgdorferi; D003165:Complement System Proteins; D019286:Endopeptidase K