The Lyme disease spirochaete, Borrelia burgdorferi, can invade and persistently infect its hosts' connective tissues. We now demonstrate that B. burgdorferi adheres to the extracellular matrix component laminin. The surface-exposed outer-membrane protein ErpX was identified as having affinity for laminin, and is the first laminin-binding protein to be identified in a Lyme disease spirochaete. The adhesive domain of ErpX was shown to be contained within a small, unstructured hydrophilic segment at the protein's centre. The sequence of that domain is distinct from any previously identified bacterial laminin adhesin, suggesting a unique mode of laminin binding.
AlitaloA.,
MeriT.,
LankinenH.,
SeppäläI.,
LahdenneP.,
HeftyP. S.,
AkinsD.,
MeriS.2002; Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs. J Immunol 169:3847–3853
BalmelliT.,
PiffarettiJ. C.1995; Association between different clinical manifestations of Lyme disease and different species of Borrelia burgdorferi sensu lato. Res Microbiol 146:329–340
BarbosaA. S.,
AbreuP. A. E.,
NevesF. O.,
AtzingenM. V.,
WatanabeM. M.,
VieiraM. L.,
MoraisZ. M.,
VasconcellosS. A.,
NascimentaoA. L. T. O.2006; A newly identified leptospiral adhesin mediates attachment to laminin. Infect Immun 74:6356–6364
BartholdS. W.,
PersingD. H.,
ArmstrongA. L.,
PeeplesR. A.1991; Kinetics of Borrelia burgdorferi dissemination and evolution of disease after intradermal inoculation of mice. Am J Pathol 139:263–273
BartholdS. W.,
de SouzaM.,
FikrigE.,
PersingD. H.1992a; Lyme borreliosis in the laboratory mouse. In Lyme Disease: Molecular and Immunologic Approaches pp 223–242 Edited by
SchutzerS. E.
Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
BartholdS. W.,
SidmanC. L.,
SmithA. L.1992b; Lyme borreliosis in genetically resistant and susceptible mice with severe combined immunodeficiency. Am J Trop Med Hyg 47:605–613
BunikisJ.,
GarpmoU.,
TsaoJ.,
BerglundJ.,
FishD.,
BarbourA. G.2004; Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe. Microbiology 150:1741–1755
CadavidD.,
BaiY.,
DailD.,
HurdM.,
NarayanK.,
HodzicE.,
BartholdS. W.,
PachnerA. R.2003; Infection and inflammation in skeletal muscle from nonhuman primates infected with different genospecies of the Lyme disease spirochete Borrelia burgdorferi
. Infect Immun 71:7087–7098
CameronC. E.,
BrouwerN. L.,
TischL. M.,
KurioiwaJ. M. Y.2005; Defining the interaction of the Treponema pallidum adhesin Tp0751 with laminin. Infect Immun 73:7485–7494
CasjensS.,
van VugtR.,
TillyK.,
RosaP. A.,
StevensonB.1997; Homology throughout the multiple 32-kilobase circular plasmids present in Lyme disease spirochetes. J Bacteriol 179:217–227
CasjensS.,
PalmerN.,
van VugtR.,
HuangW. M.,
StevensonB.,
RosaP.,
LathigraR.,
SuttonG.,
PetersonJ.other authors2000; A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs of an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi
. Mol Microbiol 35:490–516
CasjensS. R.,
HuangW. M.,
GilcreaseE. B.,
QiuW.,
McCaigW. D.,
LuftB. J.,
SchutzerS. E.,
FraserC. M.2006; Comparative genomics of Borrelia burgdorferi
. In Molecular Biology of Spirochetes pp 79–95 Edited by
CabelloF. C.,
HulinskaD.,
GodfreyH. P.
Amsterdam: IOS Press;
CrotherT. R.,
ChampionC. I.,
WhiteleggeJ. P.,
AguileraR.,
WuX. Y.,
BlancoD. R.,
MillerJ. N.,
LovettM. A.2004; Temporal analysis of the antigenic composition of Borrelia burgdorferi during infection in rabbit skin. Infect Immun 72:5063–5072
CunninghamT. M.,
ThomasD. D.,
ThompsonS. D.,
MillerJ. N.,
LovettM. A.1988; Identification of Borrelia burgdorferi surface components by Triton X-114 phase partitioning. Ann N Y Acad Sci 539:376–378
DasS.,
BartholdS. W.,
Stocker GilesS.,
MontgomeryR. R.,
TelfordS. R.,
FikrigE.1997; Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host. J Clin Invest 99:987–995
DefosseD. L.,
DurayP. H.,
JohnsonR. C.1992; The NIH-3 immunodeficient mouse is a model for Lyme borreliosis myositis and carditis. Am J Pathol 141:3–10
De KoningJ.,
BosmaR. B.,
Hoogkamp-KorstanjeJ. A.1987; Demonstration of spirochaetes in patients with Lyme disease with a modified silver stain. J Med Microbiol 23:261–267
EdwardsA. M.,
JenkinsonH. F.,
WoodwardM. J.,
DymockD.2005; Binding properties and adhesion-mediating regions of the major sheath protein of Treponema denticola ATCC 35405. Infect Immun 73:2891–2898
FischerJ. R.,
LeBlancK. T.,
LeongJ. M.2006; Fibronectin binding protein BBK32 of the Lyme disease spirochete promotes bacterial attachment to glycosaminoglycans. Infect Immun 74:435–441
FranzJ. K.,
FritzeO.,
RittigM.,
KeyßerG.,
PriemS.,
ZacherJ.,
BurmesterG. R.,
KrauseA.2001; Insights from a novel three-dimensional in vitro model of Lyme arthritis. Arthritis Rheum 44:151–162
GilmoreR. D.Jr,
MbowM. L.,
StevensonB.2001; Analysis of Borrelia burgdorferi gene expression during life cycle phases of the tick vector Ixodes scapularis
. Microbes Infect 3:799–808
HäuplT.,
HahnG.,
RittigM.,
KrauseA.,
SchoernerC.,
SchonherrU.,
KaldenJ. R.,
BurmesterG. R.1993; Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Arthritis Rheum 36:1621–1626
HeftyP. S.,
JolliffS. E.,
CaimanoM. J.,
WikelS. K.,
AkinsD. R.2002; Changes in the temporal and spatial patterns of outer surface lipoprotein expression generate population heterogeneity and antigenic diversity in the Lyme disease spirochete, Borrelia burgdorferi
. Infect Immun 70:3468–3478
HellwageJ.,
MeriT.,
HeikkiläT.,
AlitaloA.,
PaneliusJ.,
LahdenneP.,
SeppäläI. J. T.,
MeriS.2001; The complement regulatory factor H binds to the surface protein OspE of Borrelia burgdorferi
. J Biol Chem 276:8427–8435
HoS. N.,
HuntH. D.,
HortonR. M.,
PullenJ. K.,
PeaseL. R.1989; Site-directed mutagensis by overlap extension using polymerase chain reaction. Gene 77:51–59
KimJ. H.,
SingvallJ.,
Schwartz-LinekU.,
JohnsonB. J. B.,
PottsJ. R.,
HöökM.2004; BBK32, a fibronectin binding MSCRAMM from Borrelia burgdorferi, contains a disordered region that undergoes a conformational change on ligand binding. J Biol Chem 279:41706–41714
KraiczyP.,
HellwageJ.,
SkerkaC.,
KirschfinkM.,
BradeV.,
ZipfelP. F.,
WallichR.2003; Immune evasion of Borrelia burgdorferi: mapping of a complement inhibitor factor H-binding site of BbCRASP-3, a novel member of the Erp protein family. Eur J Immunol 33:697–707
KurtenbachK.,
HanincovaK.,
TsaoJ. I.,
MargosG.,
FishD.,
OgdenN. H.2006; Fundamental processes in the evolutionary ecology of Lyme borreliosis. Nat Rev Microbiol 4:660–669
LamT. T.,
NguyenT.-P. K.,
MontgomeryR. R.,
KantorF. S.,
FikrigE.,
FlavellR. A.1994; Outer surface proteins E and F of Borrelia burgdorferi, the agent of Lyme disease. Infect Immun 62:290–298
LaneR. S.,
PiesmanJ.,
BurgdorferW.1991; Lyme borreliosis: relation of its causative agent to its vectors and hosts in North America and Europe. Annu Rev Entomol 36:587–609
McDowellJ. V.,
SungS. Y.,
PriceG.,
MarconiR. T.2001; Demonstration of the genetic stability and temporal expression of select members of the Lyme disease spirochete OspF protein family during infection in mice. Infect Immun 69:4831–4838
MettsM. S.,
McDowellJ. V.,
TheisenM.,
HansenP. R.,
MarconiR. T.2003; Analysis of the OspE determinants involved in binding of factor H and OspE-targeting antibodies elicited during Borrelia burgdorferi infection. Infect Immun 71:3587–3596
MillerJ. C.,
StevensonB.2006; Borrelia burgdorferi erp genes are expressed at different levels within tissues of chronically infected mammalian hosts. Int J Med Microbiol 296 :Suppl. 1185–194
MillerJ. C.,
von LackumK.,
BabbK.,
McAlisterJ. D.,
StevensonB.2003; Temporal analysis of Borrelia burgdorferi Erp protein expression throughout the mammal-tick infectious cycle. Infect Immun 71:6943–6952
MillerJ. C.,
von LackumK.,
WoodmanM. E.,
StevensonB.2006; Detection of Borrelia burgdorferi gene expression during mammalian infection using transcriptional fusions that produce green fluorescent protein. Microb Pathog 41:43–47
PachnerA. R.,
BastaJ.,
DelaneyE.,
HulinskaD.1995; Localization of Borrelia burgdorferi in murine Lyme borreliosis by electron microscopy. Am J Trop Med Hyg 52:128–133
ProbertW. S.,
JohnsonB. J. B.1998; Identification of a 47 kDa fibronectin-binding protein expressed by Borrelia burgdorferi isolate B31. Mol Microbiol 30:1003–1015
RadolfJ. D.,
ChamberlainN. R.,
ClausellA.,
NorgardM. V.1988; Identification and localization of integral membrane proteins of virulent Treponema pallidum subsp. pallidum by phase partitioning with the nonionic detergent Triton X-114. Infect Immun 56:490–498
SeinostG.,
DykhuizenD. E.,
DattwylerR. J.,
GoldeW. T.,
DunnJ. J.,
WangI. N.,
WormserG. P.,
SchrieferM. E.,
LuftB. J.1999; Four clones of Borrelia burgdorferi sensu stricto cause invasive infection in humans. Infect Immun 67:3518–3524
ShihC.-M.,
PollackR. J.,
TelfordS. R.,
SpielmanA.1992; Delayed dissemination of Lyme disease spirochetes from the site of deposition in the skin of mice. J Infect Dis 166:827–831
SkareJ. T.,
FoleyD. M.,
HernandezS. R.,
MooreD. C.,
BlancoD. R.,
MillerJ. N.,
LovettM. A.1999; Cloning and molecular characterization of plasmid-encoded antigens of Borrelia burgdorferi
. Infect Immun 67:4407–4417
StevensonB.,
TillyK.,
RosaP. A.1996; A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31. J Bacteriol 178:3508–3516
StevensonB.,
BonoJ. L.,
SchwanT. G.,
RosaP.1998; Borrelia burgdorferi Erp proteins are immunogenic in mammals infected by tick bite, and their synthesis is inducible in cultured bacteria. Infect Immun 66:2648–2654
StevensonB.,
ZückertW. R.,
AkinsD. R.2001; Repetition, conservation, and variation: the multiple cp32 plasmids of Borrelia species. In The Spirochetes: Molecular and Cellular Biology pp 87–100 Edited by
SaierM. H.,
García-LaraJ.
Oxford: Horizon Press;
StevensonB.,
El-HageN.,
HinesM. A.,
MillerJ. C.,
BabbK.2002; Differential binding of host complement inhibitor factor H by Borrelia burgdorferi Erp surface proteins: a possible mechanism underlying the expansive host range of Lyme disease spirochetes. Infect Immun 70:491–497
StevensonB.,
BykowskiT.,
CooleyA. E.,
BabbK.,
MillerJ. C.,
WoodmanM. E.,
von LackumK.,
RileyS. P.2006; The Lyme disease spirochete Erp lipoprotein family: structure, function and regulation of expression. In Molecular Biology of Spirochetes pp 354–372 Edited by
CabelloF. C.,
GodfreyH. P.,
HulinskaD.
Amsterdam: IOS Press;
ThompsonJ. D.,
GibsonT. J.,
PlewniakF.,
JeanmouginF.,
HigginsD. G.1997; The clustal_x Windows interface: flexible strategies for multiple sequence alignment aided by quality analyses tools. Nucleic Acids Res 25:4876–4882
van DamA.P.,
KuiperH.,
VosK.,
WidjojokusumoA.,
de JonghB. M.,
SpanjaardL.,
RamselaarA. C. P.,
KramerM. D.,
DankertJ.1993; Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. Clin Infect Dis 17:708–717
WangG.,
OjaimiC.,
IyerR.,
SaksenbergV.,
McClainS. A.,
WormserG. P.,
SchwartzI. A.2001; Impact of genotypic variation of Borrelia burgdorferi sensu stricto on kinetics of dissemination and severity of disease in C3H/HeJ mice. Infect Immun 69:4303–4312
WangG.,
OjaimiC.,
WuH.,
SaksenbergV.,
IyerR.,
LiverisD.,
McClainS. A.,
WormserG. P.,
SchwartzI.2002; Disease severity in a murine model of Lyme borreliosis is associated with the genotype of the infecting Borrelia burgdorferi sensu stricto strain. J Infect Dis 186:782–791
ZambranoM. C.,
BeklemishevaA. A.,
BryskinA. V.,
NewmanS. A.,
CabelloP. C.2004; Borrelia burgdorferi binds to, invades, and colonizes native type I collagen lattices. Infect Immun 72:3138–3146