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Borrelia species

1. 3-20 x 0.2-0.5 um, more irregular than treponemes


2. Can be stained in appropriate specimens (e.g. blood)
using Giemsa
3. Number of axial filaments depends on species (e.g. 12
for B. recurrentis)
4. Microaerophlic, nutritionally fastidious but grow
slowly in vitro
5. Either louse-borne (B. recurrentis) or tick-borne (e.g.
B. hermsii, B. perkeri, B burgdorferi, etc.)
6. Currently 18 recognized species
7. Cause relapsing fevers or Lyme disease

Relapsing fever Borrelias


1. Possess a linear chromosome and plasmids (up to 14
plasmids per bacterial cell
2. Tick is the vector and injects bacteria into bloodstream
after biting
3. Disseminated throughout the body
4. Causes high fever approx. 5-7 days post-infection,
followed by subsidence and then subsequent relapse with
fever.
5. Cycle may continue hence the name relapsing fever

Relapsing fever Borrelias (contd.)


6. Demonstrate antigenic variation
7

10
Sero. 21

10
Sero. 7

Anti 7

10
Sero 14.

Anti21

1.5

#s Borrelia
Serotype
specific IgM
Anti14

2.5
Weeks post infection

Relapsing fever Borrelias (contd.)

7. Variation are in the variable major proteins (VMP) of the


outer membrane. Two families of proteins - variable small amd
variable large protein (Vsp and Vlp respectively)
8. Vsp (20kDa) and Vlp (36kDa) are lipoproteins anchored to
the membrane via their lipids
9. VMPs may be involved in tissue tropism

10. Clearing in vivo occurs through complement-mediated lysis


11. The genes encoding the VMPs are located on plasmids and the
chromosome.
12. A single bacterial cell can only express one antigenic type of
VMP
13. How are genes activated to alter the antigenic profile of a
bacterium?

p
p
p
p

p
p

p
p
p
p

Barbour & Restrepo (2000): Emerging Inf. Dis.6:451

VMP gene structure


1. The genes encoding the VMPS (vlp and vsp genes)
share common properties facilitating recombinaion.
5
Constant

3
Variable

Constant

2. Upstream homology region is 50bp from 5 region


3. Downstream homology site is 1kbp from 3 end of gene

Borrelia direct repeat (Bdr) proteins


1. Bdr genes are found in all Borrelias
2. Sequence analysis indicates conserved functionaldomains

3. Precise function is unknown; signaling molecules??

Epidemiology of relapsing fever


1. Seasonal incidence in the US
2. Associated with campers, backpackers, etc.
3. Humans are incidental hosts for most relapsing fever
Borrelias
4. Transmission by infected tick bite
5. B. recurrentis is a louse-borne disease of humans with
interhuman transmission
6. Endemic in underdeveloped countries and associated with
poverty and overcrowding

Lyme disease borreliosis


1. Caused by B. burdorferi
2. First recognized in 1977 among children in Lyme, Conn.
believed to be suffering from rheumatoid arthritis
3. Begins as a localized skin infection but may spread as a
second phase after latency involving multiple system (c.p.
syphilis)
4. Reservoir of infection - Infected animals (deer & mice)
Tick (Ixodes dammini) vector

Borrelia burdorferi
1. Long slender spirochetes (20-30 x 0.2-0.3 microns)
2. 7-11 axial filaments
3. Possesses a linear chromosome as well as linear and
circular plasmids
4. Does not demonstrate extensive antigenic variability
5. Linear plasmids encode two major outer surface
lipoproteins, OspA and OspB.

B. burgdorferi Virulence
1. Initial adherence to host tissues
In vitro B. burgdorferi bind to many cell types via
integrins and glycosaminoglycans.
2. Multiple binding pathways or a single promiscuous
pathway?
3. Observed binding specificities among different strains
of B. burgdorferi may indicate differences in binding
components

B. burgdorferi virulence contd.


4. Infection is frequently characterized by bacteria/ECM
association.
5. Decorin is a host-cell, collagen-associated protein to which
B. burgdorferi binds
6. Two bacterial porteins, DbpA and DbpB, mediate
adherence to decorin

DbpA and B
1. Encoded by a large (approx. 54kbp) linear plasmids
2. Outer membrane proteins
3. Not homologous to other known adhesins
4. Following invasion into the connective tissue these
proteins may play a role in establishment and spread of
bacteria.
5. Have been considered as immunogens for
vaccination.
6. Decorin regulates collagen fibril formation,
inactivation of C1q, cell growth, etc.
7. Dbps could play a role in mediating inflammation

Interaction with finbrocytes


1. Fibrocytes express fibronectin and collagen, they target to
connective tissue and recruit T cells. Therefore, they may play
a role in mediating inflammation in connective tissue
2. B. burgdorferi bind, in vtiro, to finbrocytes
3. Bacteria reside deep within membrane invaginations
without being phagocytosed
4. Location of binding may protect bacteria from immune
system
5. Bacteria may coat themselves in host cell membrane (i.e.
mimicry)

Epidemiology
1. One of the most common spirochetal diseases in US

CDC, 2000

Epidemiology contd.
2. Seasonal incidence

CDC, 2000

Epidemiology contd.
3. Most cases are associated with the eastern seaboard
states, upper midwest, and west
4. Most reliable clinical marker is the erythema migrans
that occurs in 60-80% of infections
5. Cases confirmed by either isolation form clinical
specimen OR demonstration of diagnostic levels of IgM
and IgG
6. LYMErix is an rOspA-based vaccine