Functional Studies Aid Fight Against Parasitic Diseases - Technology Networks

Posted: 25 Feb 2020 01:42 AM PST

In the quest to develop more effective treatments for parasitic diseases like African sleeping sickness, Chagas disease and Leishmaniasis, scientists look for weaknesses in the organisms' molecular machinery. These weaknesses can then be targeted with drug therapies designed to kill the parasites.

While they've made significant strides in recent years, scientists are still trying to unravel how the parasites' complex molecular systems work. A team of Clemson University College of Science researchers recently contributed to that understanding by discovering the function of a specific protein in the three related parasites — Trypanosama brucei, Trypanosoma cruzi and Leishmania — which afflict millions worldwide and are sometimes fatal.

According to genetics and biochemistry associate professor Meredith Morris, the parasites share some of the same molecular makeup as humans, so drugs that can kill the parasites often do harm or have adverse side effects to the human hosts.

"We are always looking for ways that the parasites differ from us," Morris said. "One of the main differences is that the parasites have a specialized cellular compartment or organelle that is absolutely essential to their survival."

Morris and her team reported their results in mSphere on Feb. 19, 2020. The title of their paper is "Trypanosoma brucei Pex13.2 is an accessory peroxin that functions in the import of PTS2 proteins and localizes to subdomains of the glycosome."

That parasite-specific organelle is called the glycosome, which plays a crucial role in cell processes, particularly energy metabolism. The glycosome organelle is surrounded by a single membrane, where several proteins reside. These proteins (Pex13.1, 13.2 and 14) import other proteins required for normal cell functioning.

In their study, Morris and her students used biochemical approaches to partially resolve the composition of those three glycosome proteins. In the process, they demonstrated that Pex13.2 is an integral glycosome membrane protein that interacts with Pex13.1 and Pex14, which was previously not known.

Utilizing the advanced microscopy technology in Clemson's Light Imaging Facility, they also obtained very high-resolution images, and found that Pex13.2 exhibits a unique localization pattern that may be critical to its function.

"No one knew what Pex13.2 was doing, but our study adds to that understanding," said Morris, a member of Clemson's Eukaryotic Pathogens Innovation Center (EPIC). "Now we know that it plays a role in import of proteins and the division of the organelles."

The team also silenced Pex13.2, which resulted in parasites with fewer, larger glycosomes. Without 13.2, the parasite couldn't import glycosome proteins, resulting in the parasite's death.

"Others have shown that when 13.2 is knocked out, the cell dies," said Morris, noting that by fully understanding the organelle's parts and functions, drug companies could someday design rational approaches to disrupting the system and killing the parasite.

In addition to Morris, the research team included lead author Logan Crowe (Ph.D. 2019), now a post-doctoral fellow at the University of Georgia; graduate student Christina Wilkinson; and Kathleen Nicholson (B.S. 2017), now a doctoral student at the University of Notre Dame.

The team credits the expertise and instrumentation of Clemson's Light Imaging Facility for enabling them to obtain high-resolution images of single glycosomes, which was critical to this work.

Reference
Trypanosoma brucei Pex13.2 Is an Accessory Peroxin That Functions in the Import of Peroxisome Targeting Sequence Type 2 Proteins and Localizes to Subdomains of the Glycosome. Logan P. Crowe, Christina L. Wilkinson, Kathleen R. Nicholson, Meredith T. Morris.mSphere, DOI: 10.1128/mSphere.00744-19.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Parasitic worms have armies, produce more soldiers when needed - National Science Foundation

Posted: 28 Feb 2020 03:14 PM PST

Research News

Parasitic worms have armies, produce more soldiers when needed

Worm societies can adjust army size to meet threat levels

In parasitic trematode worms, small members of a colony are poised to attack competing worms.

February 28, 2020

In estuaries around the world, tiny trematode worms take over the bodies of aquatic snails. These parasitic flatworms invade the snails' bodies and use them to support the worm colony, sometimes for more than a decade, "driving them around like cars," according to Ryan Hechinger, a scientist at California's Scripps Institution of Oceanography.

Like many other highly organized animal societies, including bees and ants, trematode colonies form castes to split the workload. Some trematodes, called reproductives, are larger and do all the reproduction for the colony, while smaller worms with larger mouths, known as soldiers, protect against outside invasion from competing trematodes.

In a new study published in Biology Letters, the research team demonstrated that the number of soldiers in a trematode colony depends on the local invasion threat, showing that such societies produce greater standing armies in areas of greater threat. The results have implications for understanding how animal societies determine their resource allocation.

"Each trematode colony is built of clones from a single invading worm," said Hechinger. "They don't want to share their snail with another trematode, so as their population takes over their host, they start producing soldiers to fight off any potential invaders."

But the real question was whether the trematodes produced more soldier worms when they lived in environments where they were more likely to encounter invaders.

To find out, the researchers collected snails at 38 sites from 12 estuaries with varying invasion threat levels along the North American Pacific coast and brought them back to the lab for analysis.

Snails collected in locations where there was a high risk of being invaded by other parasites had larger numbers of soldier worms poised to attack a new threat.

The sampling effort, funded by the National Science Foundation, included counting trematode worms from six separate species. All but one showed the same pattern of more soldiers in response to higher risk, indicating that this trait is generalizable among trematode species, families and even orders, providing support that this may be true for other animal societies.

"Trematodes are the cause of several serious human diseases," said Sam Scheiner, a program director in NSF's Division of Environmental Biology. "Understanding their biology is critical for disease control."

-- NSF Public Affairs, researchnews@nsf.gov

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