This article was originally published by the IU College of Arts + Sciences on June 30, 2026.
Every year bacteria kill more than a million people worldwide through infections that no longer respond to antibiotics. In many cases, why those bacteria are so hard to stop comes down to their uniquely powerful structure.
On the surfaces of many disease-causing bacteria, fibers thousands of times thinner than a human hair bristle, acting like biological grappling hooks. These fibers help bacteria latch onto body tissue, build biofilms, which are sticky bacterial communities that antibiotics struggle to penetrate, and reel in fragments of DNA from their environment, including genes that help them resist drugs.
Now, scientists in the College of Arts and Sciences at Indiana University Bloomington, with colleagues from Dartmouth College and the Georgia Institute of Technology, have solved a key mystery about how those hooks work. A new study, published in the Proceedings of the National Academy of Sciences, reveals the molecular mechanism behind one of the most powerful mechanical actions in all of biology, the reeling in of tiny surface fibers called type IV pili.
The findings shed light on how bacteria pull off this feat with such extraordinary force, and may point toward new ways to interfere with the resistance process in disease-causing species.
Type IV pili are whip-like fibers that extend from the outer surface of many bacteria, and are then reeled in at a force that ranks among the most powerful movements ever recorded in any living thing. The ability of these fibers to be reeled in is central to how bacteria make us sick.
For example, when Pseudomonas aeruginosa infects the lungs of a cystic fibrosis patient, it uses pili to grip the airway lining and hold on. When Neisseria gonorrhoeae colonizes the uro-genital tract, pili help it stick and multiply. And inVibrio cholerae, the bacterium that causes cholera, the focus of this study, pili reel in fragments of DNA from the environment, including genes that give bacteria resistance to antibiotics, akin to a fishing rod pulling in a line.
That last function, which scientists call horizontal gene transfer, is one of the main engines driving the global antibiotic resistance crisis. Why? Because bacteria do not have to evolve resistance on their own. They can simply grab it from other bacteria, whether those bacteria are dead or alive, using their pili as fishing lines.
“These tiny molecular motors are some of the strongest in nature, and understanding how they coordinate their activities to achieve such force is something the field has been working toward for a long time,” said Abigail Teipen, lead author of the study and a graduate student in the Biology department in the College at IU Bloomington.
Scientists already knew that snapping a pilus back requires two motor proteins, called PilT and PilU, working in tandem inside the bacterial cell. What still needed to be determined was why both were needed, and how they coordinated at the molecular level.
To solve the puzzle, the study co-authors used a leading-edge computer modeling tool, AlphaFold 3, which predicts how proteins fit together. The team modeled the interaction between PilT, PilU, and a third protein called PilC, which anchors the whole motor system to the pilus machine.
The models revealed a clear division of labor. PilT is the essential connector, anchoring the whole motor system to the pilus machine and which simultaneously holds PilU in place. But PilU cannot get there on its own. Once both proteins lock in, they stack on top of each other, and a unique tail on PilU wraps around PilT like a hand gripping a handle, which may allow the two motors to move as one. The team also ran molecular dynamics simulations, high-powered computer animations of atoms in motion, to watch the two motors interact in real time over hundreds of nanoseconds. Those simulations helped confirm exactly which molecular contacts hold PilT and PilU together.
The researchers then validated those predictions through rigorous lab experiments, deliberately altering specific molecular contact points and watching what happened to bacterial behavior. Breaking the PilT-PilU connection did not kill the bacteria outright, but it did stop them from pulling in DNA the way they otherwise would.
“The results show that it is not just having two motors that matters, it’s how they physically interact and coordinate,” said Ankur Dalia, Professor of Biology and senior author of the study. “If we can find ways to disrupt that coordination, we may have a new avenue for stopping bacteria from spreading antibiotic-resistant genes and establishing infections.”
The researchers calculated that one motor protein working alone should top out at roughly 50 piconewtons of force, an almost incomprehensibly small unit of measurement, yet for a structure millions of times smaller than anything visible to the naked eye, this is a remarkable amount of power. Still, pili in living bacteria have been measured pulling at more than twice that force. This suggests that the PilU tail wrapping around PilT allows the two motors to synchronize their energy cycles to pull pili at a force that neither motor could achieve alone.
One of the study’s significant findings is that this coordination mechanism is not unique to cholera bacteria. The same key molecular contact was found in Acinetobacter baylyi, a distantly related species, and sequence analysis suggests it is broadly conserved across many disease-causing bacteria, including Pseudomonas aeruginosa and Legionella pneumophila, which causes Legionnaires’ disease. That conservation suggests the coordination strategy evolved early and has been preserved because it is essential to bacterial survival.
The research was funded by the National Institutes of Health.
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