How the most widespread parasite on Earth reads its genome Swati Mestri Scientific Editor Robert Egan Senior Editor A parasite carried by billions of people worldwide often causes harmful infections during pregnancy and in immunocompromised individuals and is a leading infectious cause of blindness in South America. Once it enters the body, it can rapidly multiply, spreading from one cell to the next. This single-celled organism, Toxoplasma gondii, belongs to the same group of microbes as the parasite that causes malaria and many other parasites of humans and animals.

Cats are Toxoplasma's main host, but it can infect most warm-blooded mammals, including humans, who typically become infected through contact with cat feces or by consuming undercooked meat or contaminated produce. The parasite's ability to survive and spread inside a host depends on its capacity to precisely control which proteins it makes and when. Proteins are the molecular machinery that carries out all of the parasite's functions, from invading and manipulating host cells to making new copies of the pathogen that spread to other cells and hosts.

This means that at different points in its life cycle, Toxoplasma must have different sets of proteins available in a tightly timed sequence so it can quickly switch between growth, replication and infection states. How the parasite stays ready Now, Whitehead Institute member Sebastian Lourido and former graduate student Dominic Schwarz have uncovered new details about how Toxoplasma controls the timing of protein production, ensuring the right molecular tools are available exactly when they are needed. Their work, published in Nature Communications, reveals that two protein complexes—groups of proteins that work together like molecular machines—manage this process.

One complex promotes the production of proteins needed for the parasite's current life stage. The other keeps instructions, or genes, for making certain proteins in a poised state—accessible but not yet active—so they are ready when the parasite shifts into a different stage or encounters new conditions. "You can think of it almost like the parasite is going through its genome, reading some instructions now and placing bookmarks on others for later," says Lourido, who is also an associate professor of biology at the Massachusetts Institute of Technology (MIT).

"This allows the parasite to quickly make complex decisions and move between different stages of infection." Before this work, scientists had identified many of the genes that enable Toxoplasma to replicate, but much less was known about the molecular systems that control when and how those instructions were used to make the corresponding proteins. Understanding these systems could guide new ways to prevent and treat parasitic infections. Two complexes, different jobs The "bookmarking" process depends on how DNA is packaged inside the parasite's cells: Long strands of DNA are wound around proteins like thread wrapped around a bobbin.

Regions that are tightly wound tend to keep protein-making instructions inaccessible, while more open regions make those instructions easier to read.