West LA Times

In a recent study published in Current Biology, UCLA biologists have shed light on the behavior of skin-penetrating nematodes, specifically Strongyloides stercoralis, in response to carbon dioxide (CO2). These findings could lead to new methods for preventing or curing infections caused by these parasites.

Globally, more than 600 million people are infected with S. stercoralis, primarily in regions with inadequate sanitation infrastructure. These nematodes are excreted in the feces of an infected host and enter the ground to await a new host. When they infect a human host, they can cause severe illnesses.

Currently, ivermectin is used to treat such infections; however, resistance to this drug is emerging among some nematode populations. This situation underscores the need for new treatments.

The UCLA research team discovered that S. stercoralis respond differently to CO2 at various stages of their life cycle. They identified neurons and a gene responsible for detecting CO2 in these parasites and demonstrated how these elements can be manipulated for further study. Since CO2 is abundant in tissues like the lungs and intestines, this discovery might help scientists target the CO2-sensing pathway to develop preventive or therapeutic measures.

“Skin-penetrating nematodes encounter high CO2 concentrations throughout their life cycle, both in fecal and soil microenvironments and inside the host body,” said Elissa Hallem, corresponding author and UCLA professor of microbiology, immunology, and molecular genetics. “Our results suggest that responses to carbon dioxide play an important role in how these parasites interact with human hosts as they pass through the different stages of their life cycle and establish an infection.”

The threadworm infection cycle starts when immature larvae are excreted from a host's feces into soil where they search for a new host. Once they find one, they penetrate through the skin, travel through the body—likely passing through the lungs—and eventually settle as adults in the small intestine.

The researchers observed that infective larvae are repelled by CO2 while noninfective larvae and adults show no significant reaction. In contrast, young nematodes migrating within the body are attracted to CO2.

“CO2 repulsion in the infective larvae may initiate host-seeking by driving them off of host feces where CO2 levels are high,” said Navonil Banerjee, a postdoctoral researcher in Hallem’s lab and first author of the study. “And CO2 attraction in worms already inside the body might direct them toward the lungs and intestines which are high in CO2.”

By exposing threadworms at different life stages to CO2 and studying their behavior, Hallem's team identified neurons expressing GCY-9 receptors necessary for detecting CO2. Removing GCY-9 inhibited this detection ability.

Identifying chemosensory mechanisms between parasitic nematodes and humans may assist scientists in designing drugs targeting these pathways. Drugs inhibiting GCY-9 could impair worm navigation within hosts by disrupting their ability to detect CO2 potentially preventing or reducing infections' severity.

This research was supported by funding from the National Institutes of Health.