Ascarosides are a class of small molecules that function as chemical signals, forming a “chemical vocabulary” for communication. These compounds are released by organisms to transmit information and influence the behavior of others, coordinating a range of biological activities. This form of communication is important for the survival and interaction of the animals that produce them. The study of these molecules provides a window into the complex social lives of these organisms.
The Source and Chemical Nature
The story of ascarosides begins with the free-living nematode Caenorhabditis elegans. This millimeter-long roundworm is a model organism for biological research, which led to the initial discovery and characterization of these signaling molecules. Scientists found that C. elegans secretes these compounds into its environment to communicate with other worms, laying the groundwork for understanding this chemical language.
Ascarosides have a modular structure. They are glycolipids, consisting of a specific sugar molecule, 3,6-dideoxysugar l-ascarylose, connected to a fatty acid-like side chain. This framework can be thought of as a key, where the ascarylose sugar is the constant handle and the fatty acid chain is the variable blade, which can be modified in length and chemical structure.
This structural variability creates the diversity of the ascaroside family, with over 300 different types identified. The fatty acid side chains are built from the breakdown of fats through a process called peroxisomal β-oxidation. These chains can then be decorated with building blocks from other metabolic pathways, creating a large library of chemical signals.
A Chemical Language for Worms
In C. elegans, ascarosides function as pheromones that regulate many aspects of their lives. These chemical messages are transmitted as complex blends, not as single molecules. The specific combination and concentration of ascarosides in a mixture determines the message being sent, dictating worm behavior and development.
One well-studied function is controlling entry into the “dauer” larval stage. When food is scarce or population density is high, worms release a specific blend of ascarosides that signals young larvae to enter this state of suspended development. Dauer larvae are stress-resistant and can survive for months without food, allowing the population to endure harsh conditions. Specific molecules like ascr#2, ascr#3, and ascr#5 are potent in inducing this state.
Ascarosides also orchestrate social and reproductive behaviors. Certain ascaroside blends act as attractants, drawing males to potential mates. For example, ascr#3, produced mainly by hermaphrodites, can influence the lifespan of other worms. Other mixtures can cause worms to aggregate in groups for feeding, while different chemical signals act as repellents, encouraging dispersal and preventing overcrowding.
Even minor changes to the chemical structure of an ascaroside can alter its biological activity, allowing for a wide range of messages to be encoded. The specific blends produced can vary depending on the sex or life stage of the worm, adding to the complexity of the information being conveyed.
Ascarosides Beyond C. elegans
While first identified in C. elegans, ascaroside communication is not limited to this species. This form of communication is widespread throughout the nematode phylum, including in many parasitic species that are threats to agriculture and human health. Diverse nematodes, from those that infect plants to those that infect animals, use this conserved chemical language.
For example, entomopathogenic nematodes, used as biological control agents against insect pests, use ascarosides like ascr#9 to regulate dispersal behaviors. Similarly, plant-parasitic species, such as the root-knot nematode Meloidogyne incognita, are repelled by many of the same ascarosides. This discovery opens new avenues for understanding the biology and life cycles of these parasitic worms.
This conservation of ascaroside signaling suggests a shared evolutionary history. Although the specific blends of ascarosides may differ between species, the underlying chemical framework remains consistent. This implies the mechanisms for producing and sensing these molecules are ancient and have been adapted for the ecological niches that different nematodes inhabit.
Applications in Science and Industry
The discovery that a wide range of nematodes, including many harmful parasites, use ascarosides to communicate has practical implications. Because this signaling system is specific to nematodes, it presents an opportunity to develop targeted control strategies that are less likely to harm other organisms. This has spurred research into applications in both agriculture and medicine.
In agriculture, knowledge of ascarosides is being used to devise novel methods for pest management. For instance, specific ascarosides that repel plant-parasitic nematodes could be applied to soil or crops, creating a chemical shield to protect plants from infection. Conversely, attractant ascarosides could be used as lures in traps to capture and remove harmful nematodes from the soil. Researchers have already filed patents for using these compounds as plant-protection agents.
In the medical field, the pathways that nematodes use to produce and detect ascarosides are being investigated as potential targets for new anti-parasitic drugs. Parasitic nematodes infect billions of people and are a major burden on livestock health. By disrupting their chemical communication, it may be possible to interfere with their development, reproduction, or ability to locate a host, offering a new approach to treating and preventing these widespread infections.