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Hookworm genome sequence helps identify drug candidates

SciDev - Wed, 22 Jan 2014 10:56 GMT
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Scientists have sequenced the genome of Necator americanus, the parasite behind around 85 per cent of human hookworm infections, giving them an unprecedented insight into the worm’s biology that could help accelerate the development of drugs, diagnostics and vaccines against it.
 
They also used the sequence of the hookworm genome to identify possible targets for drugs and vaccines, publishing their findings in Nature Geneticsthis week (19 January).
 
Hookworms are responsible for neglected tropical diseases that affect 700 million people in poor communities. Infection with N. americanus leads to anaemia, malnutrition in pregnant women and impairment of children’s cognitive and physical development.
 
With treatment failure due to drug resistance already becoming a challenge for current anti-hookworm therapies, new interventions are needed, the paper says.
 
But the lack of the parasite’s complete genetic sequence has hampered the hunt for new approaches, scientists say.
 
One example is a family of proteins known as SCP/TAP, which are involved in host-parasite interactions.
 
They “have been studied as potential candidates for developing treatments” says Makedonka Mitreva, corresponding author from The Genome Institute at Washington University, United States.
 
“However, the full complement and the complexity of their gene family was not known.”
 
The study identified 96 of these proteins specific to N. americanus, which could be potential drug or vaccine targets.
 
Stefan Geiger, an immunologist at the Federal University of Minas Gerais, Brazil, welcomes the study.
 
“This information will reveal the parasite’s essential functions and allow the design of much-needed substances for humans that [act specifically] against this organism,” he says.
 
The researchers also used the new data on the hookworm’s protein kinases, a group of enzymes that regulate many cell processes, to screen existing drugs and inhibitors for potential drugs. The highest-scoring substance was a molecule approved for treating a form of the cancer leukaemia, but 233 other compounds also proved promising, the paper says.
 
Identifying existing drugs that can also be used to treat hookworm is an inexpensive way to obtain substances to turn into much-needed drugs, especially for use in developing countries, says Mitreva.
 
“Decoding the Necator americanus genome is just the start of the postgenomic era in hookworm research,” Mitreva adds.
 
The researchers also provided an example of how the genome sequence can now be used to develop more-nuanced knowledge about the pathogen. 
 
They created a microarray of 564 proteins the genome codes for and tested it against the blood of 200 individuals from Minas Gerais state in Brazil. This allowed them to identify 22 antigens, parts of these proteins, to which immune systems responded to, as well as to see how different individuals’ immune systems responded differently.
 
“This approach is important because it allows us to compare immune responses based on distinct infection profiles — such as age, duration of infection, parasitic load, history of exposure and genetic background — and identify different antigens,” says Geiger.
 
Link to paper in Nature Genetics

References

Nature Genetics doi:10.1038/ng.2875 (2013)

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