A S. stercoralis infective larva is seen on the microscopic stage. Credit score: Ruhi Patel
Threadworms, that are a kind of parasitic nematode, spend lots of time crawling round on human pores and skin, poking and prodding to seek out the perfect place for entry earlier than burrowing in. However disrupting a specific dopamine-sensing pathway causes them to lose curiosity, UCLA neurobiologists mentioned in a paper revealed in Nature Communications.
In people, dopamine is related to pleasure and reward. In parasitic worms, the identical molecule is related to the drive to penetrate pores and skin. With out dopamine signaling, the worms nonetheless crawl on the pores and skin’s floor however not often try and burrow into the pores and skin. The researchers imagine a topical preparation that disrupts this dopamine pathway may forestall an infection and be used equally to the best way that DEET mosquito sprays forestall mosquito bites.
Globally, over 600 million individuals are contaminated with the skin-penetrating threadworm, Strongyloides stercoralis, principally in tropical and subtropical areas with poor sanitation infrastructure. The worm is excreted from an contaminated host in feces after which enters the bottom to attend for a brand new host.
When a canine or human walks over or touches the infested floor, the worm, which is about half the dimensions of a pencil tip at this stage (0.5 mm), enters the host via the pores and skin to finish a sophisticated life cycle and set up an an infection, which may trigger critical sickness for the host.
What researchers wanted to find out about nematodes
“Before we started this, the worms were known to go into the skin head-first. But beyond that, basically nothing was known about the behaviors that they execute to allow them to get into the skin,” mentioned corresponding creator Elissa Hallem, a UCLA professor of microbiology, immunology and molecular genetics.
Hallem research the sensory pathways within the threadworm that assist it transfer via its life cycle and allow it to seek out and infect hosts. Earlier this 12 months, her lab found that the nematodes reply otherwise to carbon dioxide at totally different levels of their life cycle, which may assist scientists discover methods to stop or remedy infections by focusing on the CO2-sensing pathway.
To review behaviors that assist the worms penetrate pores and skin, UCLA postdoctoral researcher Ruhi Patel put them on samples of rat pores and skin and human pores and skin and recorded what they did via a microscope. The nematodes had undergone genetic manipulation to make them fluorescent, which was important for with the ability to visualize the in any other case translucent worms on the pores and skin floor.
A Strongyloides stercoralis threadworm explores and finally penetrates a pattern of human pores and skin. Credit score: Ruhi Patel
How the nematodes reacted
Patel discovered that the worms penetrated rat pores and skin in a short time, however they spent as much as 10 minutes exploring human pores and skin to seek out simply the correct spot earlier than burrowing in. When Patel repeated the experiment with a intently associated species of rat-parasitic nematode, she discovered that it penetrated each human and rat pores and skin however was much less efficient on human pores and skin, penetrating it solely 40% of the time. This implies that though each sorts of parasitic worms can penetrate host and non-host pores and skin, they’ve behaviors particular to host pores and skin that enhance their probabilities of efficiently coming into it.
“It seems like some parts of the human skin are easier for them to get into than others, and it looks like they’re kind of sampling the skin surface, trying to find a spot where they can get in more easily,” mentioned Patel. “Without these skin-probing behaviors, the parasites are less successful at entering the skin.”
When the researchers edited the S. stercoralis genome to disrupt the gene encoding a particular ion channel known as TRP-4, which features within the neurons that launch dopamine, the threadworms virtually solely did not penetrate the pores and skin. The TRP-4 channel is discovered not solely in threadworms but additionally in hookworms, one other skin-penetrating human-parasitic nematode that’s widespread in elements of the USA. Nevertheless, the TRP-4 channel is absent in people.
Based mostly on their findings, the researchers now posit that blocking the perform of the TRP-4 channel may very well be an essential mechanism for nematode management. Since people lack this channel, there can be a really low danger to our personal dopamine-sensing pathway. The researchers hope that topical lotions or lotions that block TRP-4 or different parts of the nematode dopamine-sensing pathway may forestall infections earlier than they even get began.
Extra data:
Ruhi Patel et al, Dopamine signaling drives pores and skin invasion by human-infective nematodes, Nature Communications (2025). DOI: 10.1038/s41467-025-62517-z. www.nature.com/articles/s41467-025-62517-z
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