Scientists identify potential drug target in blood-feeding hookworms

March 22, 2018, Public Library of Science
N. brasiliensis L3 fed with APC labelled RBC (anti-Ter119). Picture shows specific uptake of RBC into the larval intestine, and the accompanying dark pigment formation. Credit: Tiffany Bouchery

In hookworms that infect and feed on the blood of mice, scientists have discovered a key step in blood digestion that can be targeted to disrupt the parasite's development and survival. These findings, published in PLOS Pathogens by Tiffany Bouchery of Malaghan Institute of Medical Research, New Zealand, and colleagues could help pave the way to new treatments against hookworms in humans.

Hookworms are parasitic worms that infect hundreds of millions of people worldwide, primarily in developing countries. Transmitted through the skin via contaminated soil, they take up residence in the intestines, where they feed on blood and cause anemia, stunted childhood development, and complications during pregnancy.

New treatments are needed to combat hookworms, and one potential strategy is to target their blood-feeding activity. From their host's blood, hookworms scavenge a molecule called heme—a molecular component of hemoglobin, which transports oxygen in the blood. Heme is toxic on its own, and many blood-feeding parasites have developed heme-detoxification mechanisms; Bouchery and colleagues hypothesized that hookworms may use a similar strategy.

The researchers performed a series of experiments using a mouse-infecting hookworm species. First, they showed that it behaves similarly to its human-infecting counterparts, feeding on blood and causing anemia in mice. Next, they found that feeding or haemoglobin to the hookworm fosters its growth and causes it to produce a dark brown pigment similar to hemozoin, the detoxified form of heme produced by many other -feeding parasites.

The scientists then tested the effects of quinolones, chemical compounds that are known to disrupt hemozoin formation in malaria and schistosoma parasites. They found that quinolones likewise disrupted production of the hemozoin-like pigment in mouse-infecting hookworms, interrupting their development and their ability to reproduce. Mice treated with quinolones had significantly lower levels of hookworms, eggs, and anemia.

Due to widespread drug resistance, quinolones are not a realistic weapon against human-infecting hookworms. However, these new findings suggest that development of other drugs or vaccines targeting heme-detoxification pathways could hold promise against human-infecting hookworms. The authors hope that "this leads to new opportunities to treat this most devastating of tropical diseases."

Explore further: Fast test can monitor drug resistance in hookworms

More information: Bouchery T, Filbey K, Shepherd A, Chandler J, Patel D, Schmidt A, et al. (2018) A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development. PLoS Pathog 14(3): e1006931. doi.org/10.1371/journal.ppat.1006931

Related Stories

Fast test can monitor drug resistance in hookworms

December 8, 2016
More than 2 billion people around the world are infected with intestinal helminths, parasitic worms that can cause disease, complicate pregnancies, and stunt the growth of children. A number of drugs are currently used to ...

Sequencing the hookworm: Ancylostoma ceylanicum genome provides potential new drug, vaccine targets

March 2, 2015
In an advance that may potentially lead to new treatments for parasitic hookworms, scientists at the University of Massachusetts Medical School and Cornell University have sequenced the genome of the hookworm, Ancylostoma ...

Asthmatics could breathe easier in the future with help from an unlikely quarter—parasitic hookworms

October 26, 2016
Asthmatics could breathe easier in the future with help from an unlikely quarter—parasitic hookworms.

Recommended for you

Antibiotic prescribing influenced by team dynamics within hospitals

November 15, 2018
Antibiotic prescribing by doctors is influenced by team dynamics and cultures within hospitals.

Discovery suggests new route to fight infection, disease

November 14, 2018
New research reveals how a single protein interferes with the immune system when exposed to the bacterium that causes Legionnaires' disease, findings that could have broad implications for development of medicines to fight ...

Zika may hijack mother-fetus immunity route

November 14, 2018
To cross the placenta, Zika virus may hijack the route by which acquired immunity is transferred from mother to fetus, new research suggests.

Maternally acquired Zika immunity can increase dengue disease severity in mouse pups

November 14, 2018
To say that the immune system is complex is an understatement: an immune response protective in one context can turn deadly over time, as evidenced by numerous epidemiological studies on dengue infection, spanning multiple ...

New research aims to help improve uptake of hepatitis C testing

November 14, 2018
New research published in Scientific Reports shows persisting fears about HIV infection may impact testing uptake for the hepatitis C Virus (HCV).

Synthetic DNA-delivered antibodies protect against Ebola in preclinical studies

November 13, 2018
Scientists at The Wistar Institute and collaborators have successfully engineered novel DNA-encoded monoclonal antibodies (DMAbs) targeting Zaire Ebolavirus that were effective in preclinical models. Study results, published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.