Biology Reference
In-Depth Information
87 channels or transporters, which represent protein classes already
recognized as anthelmintic targets for compounds, including macrocy-
clic lactones, levamisoles, and amino-acetonitrile derivatives (AADs).
Moreover, at least 225 genes predicted to be essential in
A. suum
are
linked to specific metabolic chokepoints, with five molecules (including
IMP dehydrogenase) representing high priority drug targets, which
warrant future evaluation. Although we have focused specifically on
essentiality
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(namely lethality) as an indicator of “druggability,” tradi-
tionally, many anthelmintic compounds have caused paralysis/paresis,
rather than directly killed the parasite, usually through the inhibition/
excitation of signaling pathways associated with contractility or loco-
motion. Such pathways are likely highly conserved among nematodes
and, thus, inhibitors of components of these pathways might have broad
applicability as drug targets. For example, a recent, post-genomic study
of receptors associated with monoaminergic signaling (linked to
decision-making processes during locomotion) in nematodes
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found
significant conservation and proposed parallel evolution for the
complement of monoamine receptors encoded by
Caenorhabditis
spp.,
B. malayi
,and
A. suum
. Additional “core” signaling and/or functional
nodes are almost certainly present in these species. Therefore,
A. suum
is
uniquely placed for investigations into the structural and functional
conservation of neuronal signaling pathways in nematodes, particularly
considering that the large size of this parasite would allow direct
investigations of neuron-specific gene transcription using RNA-Seq.
Such investigations could have major implications for anti-nematode
drug discovery.
In conclusion, characterizing the
A. suum
genome has identified
a broad range of key classes of molecules, with major relevance to
understanding the molecular biology of
A. suum
, shedding new light on
the exquisite complexities of the host
parasite interplay on an immu-
nobiological level, and paving the way for future fundamental molecular
explorations, with unique prospects of designing newmethods to control
one of the world's most important parasitic nematodes. Clearly, an
integrated use of -omic technologies will now underpin future investi-
gations of the systems biology of
A. suum
and ascariasis on a scale not
possible previously, and will provide unprecedented prospects for
developing new diagnostic and intervention strategies. This focus is now
crucial, given the major impact of
Ascaris
and other soil-transmitted
helminths, which affect billions of people and animals worldwide.
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Although these parasites are seriously neglected, particularly in terms of
funding for fundamental research and the development of new drugs,
vaccines, and diagnostics, genomic and other -omic technologies provide
new hope for the discovery of new and improved interventions against
ascariasis.
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