This is a brief research review on the relationship between B. malayi and the gram negative bacteria, wolbachia.

1. The filarial nematode, Brugia malayi and the
endosymbiotic bacteria, Wolbachia within the
mammalian host
VANESSA CHAPPELL
SYMBIOTIC ASSOCIATIONS FALL 2016

2. Multi-level symbiosis
Host
Humans and many other mammals have
complicated digestive tracts making
them ideal hosts to parasites
Parasite
Filarial Nematodes -Threadlike
adult filarial worms reside in
lymphatic or subcutaneous tissues.
Offspring (microfilariae) circulate
in blood or migrate through tissue.
Endosymbiont
Wolbachia is a bacteria which
infects arthropod species and
some nematodes. In some cases
the host species cannot reproduce,
or even survive, without it.

3. The Vector

4. Microfilaria on blood smear

5. Detection of Wolbachia in larval and tissue stage B.
malayi by immunohistology
Shows wolbachia within the nematode while inside
the mosquito vector
Shows Wolbachia prevelance within nematode while
inside the mammalian host

6. Treatments with combination therapies of
ivermectin, diethlycarbamazine, and Albendazole
 Adverse effects of conventional therapy are great. When the parasites are
killed the Wolbachia bacteria can cause severe inflammatory responses
 Patient compliance low due to these effects
 Patient immune response varies depending on genetics
 Cost of treatment is high for low income societies where disease is
prevelant

7. Effects of doxycycline exploit a co-
dependant pathway
 The mechanism of action for the antibacterial effect relies on disrupting
protein translation in bacteria, thereby damaging the ability of microbes to
grow and repair thus inducing apoptosis
 Doxycycline kills the gram negative bacteria, Wolbachia, that reside in the
reproductive tract of the female nematode making them sterile.

8. Glycolosis as a co-dependant pathway
Doxycycline is also used in "tet-on" (gene expression
activated by doxycycline) and "tet-off" (gene expression
inactivated by doxycycline)

9. Results
 Results suggest that the strain of
Wolbachia found in B. malayi lacks the
genes for two glycolytic enzymes—6-
phosphofructokinase and pyruvate
kinase, rendering it unable to complete
glycolysis on their own.

10. Results
 Doxycycline interferes
with protein production
 Disruption of
Wolbachia protein
production resulted in a
decline of bacteria
fitness which in turn
increase the amounts
of glucose and
glycogen present in the
filarial parasites.

11. Discussion
 Conventional treatments with broad spectrum dewormers cause the adult
worms to become paralyzed and sterile. The worms are processed through
the patients lymphatic system where the Wolbachia bacteria are released
into the patients system causing adverse reactions. The severity of the
reactions is dependant on the individuals immune response
 After extended treatment with tetracyclines patients tested negative for
B.malayi. This decline of bacterial fitness is thought to be the cause in the
drastic reduction in filarial nematode microfilaria release.
 Interestingly, in arthropods Wolbachia is a parasitic symbiont that affects
reproduction and development. However, in filarial nematodes, Wolbachia
is a mutualistic symbiont and is required for normal development,
reproduction and even survival.

12. Works Cited
Denis Voronin, Saheed Bachu, Michael Shlossman, Thomas R. Unnasch, Elodie Ghedin, Sara Lustigman.
2016. "Glucose and Glycogen Metabolism in Brugia malayi Is Associated with Wolbachia
Symbiont Fitness." PLOS ONE http://dx.doi.org/10.1371/journal.pone.0153812.
Fischer, P,, S.M. Erickson, K, Fischer, J.F. Fuchs, R.U. Rao, B.M. Christensen, and G.J. Weil. 2004.
"Persistence of Brugia Malayi DNA in vector and non-vector mosquitos; implication for
xenomonitoring and transmission monitoring of lymphatic filarisis." American Journal of Tropical
Medicine Hygiene 502-507.
Hoerauf A, Mand S, Fischer K, et al. 2003. "Doxycycline as a novel strategy against bancroftain filariasis-
depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilarial
production." Med. Microbial. Immunol 211-216.
Rao, R.U. 2005. "Endosymbiotic Wolbachia of parasitic filarial nematodes as drug targets." The Indian
Journal of Medical Research 199-204.
Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A. 2005. "Macrofilaricidal activity
after doxycycline treatment of Wuchereria bancrofti; a double blind, randomised placebo-
controlled trial." Lancet 2116-21.