Post by Ariela Schnyer & Lesly Zapata
Introducing You to
the Wolbachia
A bacteria that feeds off of a
mosquito? Can you say the Dracula of Draculas? Have no fear humans, for once
this bacteria Wolbachia pipientis is
not interested in manipulating us! Rather, these gram-negative microbes infect
arthropods,[1]
including various insects like mosquitoes, and create a fascinating symbiotic
relationship with their hosts.
More than simply being the least
scary Dracula story, Wolbachia’s
symbiotic relationship with mosquitos could provide insight into how to decrease
mosquito populations, which may in turn decrease the spread of diseases such as
Dengue fever and Chikungunya. Dengue is a mosquito-borne tropical disease that
causes flu-like symptoms and has caused high number of illness among children
in Latin America and Asia.[3]
Chikungunya, similarly caused by insects, causes fever and joint paint.[4]
Although we have an understanding
of the outcomes that result from the relationship between this bacteria and
arthropods, the underlying mechanism remains unclear. A new study by Brazilian
researchers da Rocha Fernandez et al. (2014)[5]
investigates the embryonic mechanisms in the interaction of Wolbachia and Aedes fluviatilis mosquito,
a neotropical mosquito that does not carry diseases under natural conditions,
thus making it a safe experimental model. This study leads to further
understanding of the process through which Wolbachia
influences embryogenesis via carbohydrate metabolic regulation in the insects
it infects.
[1] Daniel
LePage, Seth R. Bordenstein, Wolbachia: Can we save lives with a great
pandemic?, Trends in Parasitology, Volume 29, Issue 8, August 2013, Pages
385-393, ISSN 1471-4922, http://dx.doi.org/10.1016/j.pt.2013.06.003.
[5] da Rocha Fernandes M,
Martins R, Pessoa Costa E, Casagrande Pacidoˆnio E, Araujo de Abreu L, et al.
(2014) The Modulation of the Symbiont/Host Interaction between Wolbachia
pipientis and Aedes fluviatilis Embryos by Glycogen Metabolism. PLoS ONE 9(6):
e98966. doi:10.1371/journal.pone.0098966
So what did they do?
So what did they do?
The researchers began by
confirming the effects of Wolbachia presence
on Aedes fluviatilis mosquito
embryogenesis at the macroscopic level. They compared two strains of the mosquito;
one infected with Wolbachia (W+) and
one without (W-) and found no significant difference between the developments
of the two strains as they were incubated over a period of two days. The
hatching rates and morphological features of both strains of larvae were
similar, confirming that this symbiotic relationship does not affect the growth
of mosquito embryos. Since other recent studies[1] have
suggested that Wolbachia interacts
with its hosts through its energy metabolism pathway and is especially reliant on
its host’s glycolytic intermediates for energy absorption, these researchers
decided to further their investigation through analysis of the glycolysis
pathways of metabolism.
They found that W+ embryos
exhibited higher levels of pyruvate kinase activity than W- embryos, despite no
significant difference in the glucose content between the two types of embryos.
There was also a higher concentration of glucose 6-phosphate (G6P) in embryos
with Wolbachia than those without. W+
embryos had peak concentration of glycogen about halfway through embryogenesis,
a peak more than twice the concentration in W- embryos, suggesting that G6P is
likely intended for glycogen synthesis (as seen in figure above).
Since the most significant
difference in the glycolytic pathway between Wolbachia containing and Wolbachia
absent embryos was in the levels of glycogen, the researchers further analyzed
the effects of glycogen synthase kinase-3 (GSK-3), a glycogen synthesizing
enzyme, in Wolbachia containing
embryos. Although they initially
silenced GSK-3 using doublestranded RNA replacements, this resulted in such
underdevelopment of the ovaries that the females were no longer able to lay
eggs. In order to analyze the effects of reduced GSK-3 on embryo development,
it was necessary to have some egg production so they reduced GSK-3 production
by 30% rather than silencing it. Here they found that (similar to in silenced
GSK-3) these altered mosquitoes showed significantly diminished abdominal
distension and decreased embryonic viability. As the following figures show,
these embryos with reduced GSK-3 exhibited nearly double the total protein
concentration and glycogen presence of non-GSK-3 reduced W+ embryos.
A particularly intriguing result
was that GSK-3-mutation also significantly increased the amount of Wolbachia in
comparison to non-GSK-3-mutated eggs. This suggests that the increased presence
of glycogen during A. fluviatilis
embryogenesis may be beneficial for Wolbachia
growth and may provide clues to the nature of their symbiotic relationship.
Since enzymes involved in the synthesis and degradation of glycogen have been
found to be absent the Wolbachia
genome, Wolbachia may be dependent on
its host’s production of glycogen for energy production. This subsequently
requires the host to increase its own production of glycogen synthesis steps,
such as pyruvate kinase, in order to produce enough glycogen for both
themselves and the Wolbachia.
This study
provides initial understanding of the symbiotic relationship between Wolbachia and some of its arthropod
hosts through a glucose metabolism. One key critique of this paper lies in some
discrepancies between results stated in the abstract and the results stated in
the rest of the paper. While the researches state in their abstract that
knocking down GSK-3 leads to lower levels of
glycogen and total protein and to reduction in Wolbachia presence, the figures and body of the paper state exactly
the opposite: that there are higher levels of glycogen and total protein in the
GSK-3-knockdown and an increase in Wolbachia
presence. Since these results are the key results of the paper and have very
different implications for Wolbachia
mechanisms of symbiosis, this is a discrepancy that needs clarification from
the authors.
There is much room for further
investigation into exactly how this symbiotic relationship has evolved and the
potential implications for mosquito control. Extended research should focus on
understanding the relationship of Wolbachia
with other arthropods, and perhaps finding pathways to use these bacteria as
ways to decrease embryo viability in mosquitos that carry disease. The results
of GSK-3 knockdown increasing Wolbachia
presence and decreasing A. fluviatilis embryo
viability are promising towards this goal and Wolbachia has already shown efficacy in decreasing mosquito
populations in Los Angeles.[2]
While Wolbachia might be one of
arthropods’ worst nightmares, they may end up saving lives around the world. It
seems like all vampires aren’t bad after all!
[1] Melnikow E,
Xu S, Liu J, Bell AJ, Ghedin E, et al. (2013) A potential role for the
interaction of Wolbachia surface proteins with the Brugia malayi glycolytic
enzymes and cytoskeleton in maintenance of endosymbiosis. PLoS Negl Trop Dis 7: e2151.
doi:10.1371/journal.pntd.0002151.
[2] Maron, D. (2015, November 3). Fighting
Mosquitoes with Mosquitoes. Retrieved November 27, 2015, from http://www.scientificamerican.com/article/fighting-mosquitoes-with-mosquitoes/
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