Globally, more than 600 million individuals are affected by the skin-penetrating threadworm known as Strongyloides stercoralis, particularly in areas of tropical and subtropical climates with inadequate sanitation systems. Scientists have discovered that these nematodes react differently to carbon dioxide throughout their life cycle, which may assist researchers in developing strategies to prevent or treat infections by focusing on the CO2-sensing mechanisms.
In the U.S., the hookworm is the most recognized skin-penetrating parasitic nematode. However, worldwide, it’s estimated that over 600 million people suffer from infections caused by the threadworm Strongyloides stercoralis. This parasite is primarily present in tropical and subtropical regions lacking proper sanitation. These skin-penetrating nematodes are expelled through the feces of infected individuals and subsequently enter the soil, waiting to infect new hosts. Upon infiltrating a new host, they can lead to severe health problems.
Currently, ivermectin is used to treat these infections, but there are signs that some nematodes are becoming resistant to this primary medication. Therefore, new treatments are necessary, and researchers from UCLA may have just discovered a vital clue to aid in their development.
In research published in Current Biology, UCLA scientists observed that the threadworms S. stercoralis react differently to carbon dioxide at various stages of their life cycle. They also identified a pair of neurons and a specific gene that help detect CO2 in these parasites, providing a foundation for future studies. Given that CO2 is plentiful in bodily tissues, such as in the lungs and intestines, this discovery might enable scientists to devise methods to prevent or treat infections by targeting the CO2 sensing pathway.
According to Elissa Hallem, a UCLA microbiology, immunology, and molecular genetics professor and the paper’s lead author, “Skin-penetrating nematodes encounter significant CO2 levels throughout their lifecycle, whether in feces, soil environments, or within the host’s body. Our findings indicate that carbon dioxide responses are crucial in how these parasites engage with human hosts during various life cycle stages, influencing infection establishment.”
The lifecycle of the threadworm initiates when immature larvae found in host feces mature into infective larvae. These larvae then move into the soil, seeking a new host. Once they have found a host and entered through the skin, the nematodes navigate through the host’s body, often passing through the lungs. They eventually reach the small intestine, where they live as adult parasites and reproduce. The larvae that emerge from their eggs are released back into the environment, restarting the cycle.
UCLA researchers discovered that infective larvae tend to avoid CO2, while non-infective larvae and adult worms show indifference. Interestingly, younger nematodes traveling within the host are attracted to CO2.
Navonil Banerjee, a postdoctoral researcher in the Hallem lab and the study’s first author, explained, “The infective larvae’s aversion to CO2 may prompt them to leave host feces, where CO2 levels are elevated, in search of a host. Conversely, CO2 attraction for worms already inside the host could help guide them toward the lungs and intestines, areas rich in CO2.”
The team led by Hallem and Banerjee examined the behavioral responses of threadworms at various life stages when exposed to CO2. They identified specific neurons responsible for detecting CO2 and observed the corresponding behaviors caused by these stimuli. The researchers pinpointed these neurons as expressing a receptor called GCY-9, which supports nematodes’ ability to sense CO2. When the gene for GCY-9 was removed, the threadworms lost their ability to detect CO2, confirming the gene’s crucial role in their behavioral reactions to carbon dioxide.
Understanding the chemosensory systems that influence the relationship between parasitic nematodes and their human hosts may provide a pathway for developing new antiparasitic medications that disrupt the CO2 sensing process. For instance, drugs that inhibit GCY-9 could hinder the parasites’ movement within the body by impairing their CO2 detection abilities, potentially preventing initial infections or lessening the severity of existing ones. Future research will continue to explore additional genes within the CO2 sensing pathway as potential targets for new antiparasitic therapies.
This research received funding from the National Institutes of Health.
