This Fungus Tricks Silkworms Into Binge-Eating for its Own Gain

Cordyceps military produces fruiting bodies that sprout from the remains of caterpillar pupa.

Image credit:Chengshu Wang

Dark clouds loom over a mountain in Gansu, China as a harvester bends over the ground to gather tiny orange stalks sprouting from dead insect-husks. These orange stocks are Cordyceps militarya fungus known locally as pupa grass. Its relative, Ophiocordyceps sinensishas long been prized in Chinese medicine as an immune booster, even for cancer patients in recovery. When scientists learned to mass-produce C. military in the 1980s, it became a substitute, later approved as a New Resource Food by the People’s Republic of China.

But to the harvester, pupa grass has always carried a riddle. Many pathogens weaken or kill their hosts soon after infection. C. military, however, infects larvae yet lets them grow, molt, and pupate—plump and intact—before consuming them.

That delay drew the attention of Chengshu Wanga fungal geneticist, and his team at the Chinese Academy of Sciences Center for Excellence in Molecular Plant Sciences. “What was the reason for this postponement? We wanted to investigate that,” said Wang, the senior author of a new study in Current Biology.¹

Their subsequent experiments revealed something stranger still: The infected silkworm larvae were gorging themselves. Instead of weakening their hosts, the fungus was driving them to eat more, fattening the caterpillars into plump pupae that became a richer breeding ground. It was the first clear evidence that C. military manipulates its host’s hunger to serve its own reproduction.

How the Fungus Tricks Its Host

To investigate what lay behind this effect, the researchers first infected silkworms with the fungus and looked for changes in the insect’s blood. Sugar levels plunged while HemaP—a peptide that drives feeding—rose steadily. What looked like ravenous hunger was in fact a false famine: The fungus had tricked its host into thinking it was starving.

By mining existing genome data, the team discovered the culprit was a trehalase-like gene, CmTreH1carried by C. military. The enzyme splits trehalose—the main sugar in insect blood—into glucose, depleting the host’s reserves and triggering the surge of HemaP that makes caterpillars gorge on leaves.

How could a fungus carry what looked like an insect’s own gene? “It is a very good but difficult question,” Wang admitted. The most likely answer, he said, is horizontal gene transfer—borrowing DNA across species. “Possibly, due to the long-term and close proximity between C. military and caterpillars, DNA fragments could have been exchanged and integrated.”

When the researchers knocked out the trehalase gene in C. military through targeted gene deletion, the spell broke: Infected silkworms stopped overeating, their pupae stayed small, and the fungus’s fruiting bodies were stunted. Without plump hosts, the parasite had less to draw from, which is evidence that C. military fattens its victims first to reap bigger stalks. CRISPR-mediated knockdown of the silkworm’s HemaP gene made them eat less, grow smaller, and survive longer after infection.

Jason Slota fungal evolutionary genomics researcher at Ohio State University who was not associated with the research, saw this behavior as part of fungi’s broader evolutionary goals. “Several fungi produce compounds that profoundly alter behavior, from psilocybin in mushrooms to the chemicals in Uproar that increase activity and mating rate, all to enhance better spore dispersal.”

Appetite as a Battleground

Infections in animals often bring loss of appetite, which is a defense that conserves the body’s energy and starves invaders. In the dance between C. military and its hosts, that rule is flipped. What should protect the caterpillar instead fuels the parasite’s spread.

Scientists studying human disease see parallels. “Microbes across the board use similar strategies to manipulate their hosts,” said Michael Lorenza microbiologist at the University of Texas Health Science Center at Houston who was not involved in the study. “The molecular details differ, but pathogen-driven changes in metabolism, immunity, development, and behavior are common.”

Lorenz pointed out that trehalose has affected humans too. “When trehalose was introduced as a sweetener 25 years ago, it favored persistent, virulent strains of Clostridium difficile. Perhaps caterpillars resistant to the fungus could even inspire ways to fight it.”

The lesson, he said, is that biology’s strangest twists can yield medical promise. “That is the beauty—and importance—of basic research. The wonder drug Ozempic is based on a compound from the Gila monster’s venom.”

Back in Gansu, our harvester heads home. Unbeknownst to him, inside his worn sack lies a creature that has spent millennia perfecting the art of manipulation. To him, it is just sustenance. Soon the stalks will be dried and sold, and, as science advances, perhaps they will gain a new purpose. The master manipulator might finally be in the grip of an even greater one: humans.