Nina Holz
Critical Concepts
Learning Issues
Due- 6/30/10
1.) How does Borrelia reside in white-footed mice and other non-human mammals (serve a
purpose)?
“Ticks, small rodents, and other non-human vertebrate animals all serve as natural reservoirs for B.
burgdorferi s.l.: the bacteria can live and grow within these hosts without causing a fatal disease. Larvae
and nymph ticks typically become infected with B. burgdorferi s.l. when they feed on small animals that
carry the bacteria in spring and summer. The pathogens remain in the tick during the developmental
changes from larva to nymph or from nymph to adult in late summer or early fall. Infected nymphs
transmit B. burgdorferi bacteria to other small rodents and other mammals through biting and sucking
blood, all in the course of their normal feeding behaviour.
Borrelia spp. multiply in mice, though mice do not get diseased nor show severe clinical signs. In Europe,
the yellow-necked mouse (Apodemus flavicoliis), the wood mouse (A. sylvaticus) and the bank vole
(Clethrionomys glareolus), to name the most common once, function as reservoirs. In the USA, the whitefooted mouse (Peromyscus leucopus) is the primary animal reservoir for B. burgdorferi and the preferred
host for larval and nymphal forms of I. scapularis, the Deer tick. Deer are the preferred host for the adult
ticks in the USA; in Europe it is the roe dear (Capreolus capreolus). Other mammals including humans
and dogs can be incidental hosts and can develop Lyme disease.
There seems to be a host specifity for the different Borrelia species: B. burgdorferi s.s. and B. afzelii e.g.
usually prefer rodents as reservoir, whereas B. garinii and B. valaisiana mainly occur in birds.
Furthermore, the tick hosts seem to be differently competent as Borrelia reservoir. In case of a high
prevalence of non-competent hosts in an area, the general risk of infection is massively reduced.”
(http://www.cvbd.org/4055.0.html)
2.) What is Salp15 protein?
“B. burgdorferi binds a tick salivary protein, Salp15, during transmission from the vector, and this
interaction facilitates infection of mice. We now show that Salp15 antiserum significantly protected mice
from B. burgdorferi infection. Salp15 antiserum also markedly enhanced the protective capacity of
antibodies against B. burgdorferi antigens, such as OspA or OspC. Mice actively immunized with Salp15
were also significantly protected from tick-borne Borrelia. In vitro assays showed that Salp15 antiserum
increased the clearance of Salp15-coated B. burgdorferi by phagocytes, suggesting a mechanism of
action. Vaccination with a vector molecule that a microbe requires for infection of the mammalian host
suggests a new strategy for the prevention of Lyme disease, and this paradigm may be applicable to
numerous arthropod-borne pathogens of medical importance.” (http://www.cell.com/cell-hostmicrobe/abstract/S1931-3128(09)00348-5)
“Ixodes scapularis salivary protein, Salp15, inhibits CD4+ T cell activation by binding to the mostextracellular domains of the CD4 molecule, potentially overlapping with the gp120-binding region. We
now show that Salp15 inhibits the interaction of gp120 and CD4. Furthermore, Salp15 prevents syncytia
formation between HL2/3 (a stable HeLa cell line expressing the envelope protein) and CD4-expressing
cells. Salp15 prevented gp120-CD4 interaction at least partially through its direct interaction with the
envelope glycoprotein. A phage display library screen provided the interacting residues in the C1 domain
of gp120. These results provide a potential basis to define exposed gp120 epitopes for the generation of
neutralizing vaccines.” (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2238774/)
3.) What are the barriers to makimg a vaccine (treatment)?
Many are financial barriers
an insufficient availability of quality data from subordinate health facilities
the unavailability of health facilities willing to carry the vaccine
low levels of health care utilization; poor reporting of data from some private providers
limitations of government resources
4.) Mice vs. Ticks….Where is the high risk areas?
Figure2: U.S. Lyme disease risk map with four
categories of risk. Black = High risk, white =
Minimal or no risk.
(http://www.cvbd.org/4055.0.html)
Figure3: Evidence of persistent infection
5.) Persistance of Borellia after antibiotics?
Results indicated that following antibiotic treatment, mice remained infected with nondividing but
infectious spirochetes, particularly when antibiotic treatment was commenced during the chronic
stage of infection.
The effectiveness of antibiotic treatment was examined in a mouse model of Lyme borreliosis. Mice were
treated with ceftriaxone or saline solution for 1 month, commencing during the early (3 weeks) or chronic
(4 months) stages of infection with Borrelia burgdorferi. Tissues from mice were tested for infection by
culture, PCR, xenodiagnosis, and transplantation of allografts at 1 and 3 months after completion of
treatment. In addition, tissues were examined for the presence of spirochetes by immunohistochemistry.
In contrast to saline solution-treated mice, mice treated with antibiotic were consistently culture negative,
but tissues from some of the mice remained PCR positive, and spirochetes could be visualized in
collagen-rich tissues. Furthermore, when some of the antibiotic-treated mice were fed on by Ixodes
scapularis ticks (xenodiagnosis), spirochetes were acquired by the ticks, as determined based upon PCR
results, and ticks from those cohorts transmitted spirochetes to naïve SCID mice, which became PCR
positive but culture negative. Results indicated that following antibiotic treatment, mice remained infected
with nondividing but infectious spirochetes, particularly when antibiotic treatment was commenced
during the chronic stage of infection.