Bacteria recreate an ancient war trick to defeat viruses

The Chinese strategist Zhuge Liang, better known as Kongming, once tricked an enemy fleet into launching a barrage of arrows at empty boats padded with straw. After the volley, his soldiers collected the arrows and fired them back, winning the day with weapons supplied by the opposition.

Twenty-one centuries later, microbiologists have uncovered a molecular echo of that famous ploy inside common gut bacteria that can defeat viruses.

Researchers from the University of Copenhagen and Huazhong Agricultural University have found that E. coli carries a previously unknown antiviral system they have named “Kongming.” Like its namesake, the defense hijacks a viral enzyme to launch a counterstrike that ultimately destroys the virus.

Their work reveals a completely new immune signaling pathway in bacteria. It also widens the catalog of phage-resistance strategies and hints at applications ranging from cancer diagnostics to next-generation antibiotic alternatives.

Turning viruses against themselves

Every virus that infects bacteria, or phage, must replicate its genetic material at breakneck speed to outpace cellular defenses. Many phages therefore inject specialized nucleotide kinases, enzymes that churn out the building blocks of DNA and RNA.

The Kongming system detects that very enzyme and forces it to synthesize a different molecule altogether: a distinctive nucleotide signal known as dITP. Once made, dITP activates a protein complex, triggering a cascade that leads the bacterial cell to self-destruct.

“We’ve discovered a new antiviral signaling pathway in bacteria that, ironically, relies on a viral enzyme to produce the alarm signal that triggers defense – just like the historical Kongming, who used the production of enemy’s own arrows against them,” said Professor Rafael Pinilla-Redondo, co-author of the study.

In short, the phage hands the bacterium the very biochemical arrow that brings about its demise.

Bacteria die to defeat viruses

Suicide might sound like an odd way to survive infection, but in bacterial colonies it can be remarkably effective.

“The bacterium sacrifices itself to stop the virus – which may sound dramatic, but it’s an incredibly effective strategy. By dying, it takes the virus down with it, preventing the infection from spreading to other bacteria in the population. It’s a bit like blowing up a bridge to stop an advancing enemy,” Pinilla-Redondo said.

Because phages must complete their replication cycles inside living hosts, the premature death of a single cell prevents the release of hundreds of viral progeny. A few sacrificial cells can protect the community – much like programmed cell death in the human immune system.

Viruses can launch counter attacks

Phages are not passive targets. The scientists observed that some viruses carry auxiliary enzymes able to degrade dITP before it reaches lethal levels, effectively cutting the alarm wires.

“Some viruses have figured out how to get around Kongming,” noted first-author Ruiliang Zhao, a doctoral candidate in Pinilla-Redondo’s lab. “They carry special enzymes that break down the molecules needed to trigger the system. It’s their way of cutting off the cables of the alarm before it goes off.”

Such counterintelligence highlights the ongoing evolutionary arms race between microbes and their viral predators, a contest that has spawned CRISPR, toxin–antitoxin modules, and now the Kongming pathway.

Kongming beyond the gut

Although initially characterized in E. coli, genetic sleuthing revealed dozens of Kongming-like operons in soil and marine bacteria across the globe. This suggests that the mechanism is not a niche curiosity but a broadly distributed archetype for bacteria to defeat viruses.

By mapping its genetic hallmarks, scientists can begin to predict which environmental microbes harbor similar systems. This information is critical for biogeochemical modeling and for developing phage therapies that must bypass native immunity.

Therapy blocked by bacteria

The rise of antibiotic resistance has rekindled interest in treating infections with phages tailored to kill specific pathogens. Yet a therapeutic phage will fail if its target bacterium possesses a potent defense like Kongming.

“To develop effective phage therapies, we need to understand the natural immune systems bacteria use to resist viral attacks,” noted Pinilla-Redondo.

Detailed knowledge of Kongming and its viral countermeasures can guide the selection, or engineering of phages that slip past bacterial alarms, improving clinical success rates.

Biotech uses for Kongming

The study’s significance is not limited to infectious disease control. Because the Kongming effector complex responds exclusively to dITP, a non-canonical nucleotide implicated in genomic instability and certain cancers, it could serve as a molecular sensor for diagnostic assays.

“Since the Kongming immune effector complex specifically responds to dITP, it could be used to detect this non-canonical nucleotide – opening the door to interesting biotechnological applications,” Zhao said.

Synthetic biologists may also harness the pathway to build programmable cell-death switches or precision gene-editing safeguards.

New bacterial immunity revealed

Over the past decade, comparative genomics has uncovered an astonishing diversity of bacterial antiviral systems, yet many remain poorly understood. Kongming demonstrates how a fresh look can rewrite assumptions.

Until now, hijacking a viral enzyme to synthesize an immune signal was a trick known only in certain viruses themselves.

The discovery shows that bacteria use viral “enemy arrows” to fight viruses, highlighting a richer immune toolkit in nature than once believed.

By turning a pathogen’s own resource into an executioner, the Kongming system offers an elegant illustration of molecular jiu-jitsu – one that not only deepens our understanding of microbial warfare but also points the way toward innovative therapies and diagnostic technologies.

The study is published in the journal Science.

—–

Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates. 

Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.

—–