Irvine, Calif., April 1, 2026 — A team of scientists from UC Irvine, UC Santa Barbara and collaborating institutions has uncovered a striking new way that harmful bacteria gain a foothold in the body: They deliver a protein into human cells that helps them move through the dense, beating barrier of airway cilia and settle into a safer place to grow. The discovery, published in Science, sheds new light on how Bordetella bacteria, the causative agent of whooping cough, colonize the respiratory tract and could open the door to better treatments, smarter vaccine design and new ways to block infection before it takes hold.
This matters because the respiratory system is built to protect us. Tiny hairlike structures called cilia constantly sweep mucus, microbes and debris out of the airways. For disease-causing bacteria, getting past that moving defense is no small feat. Yet some pathogens still manage to cling on, multiply and cause illness. The new study helps explain how they do it, revealing that these bacteria are not simply sticking to the outside of cells. Instead, they appear to deploy a specialized protein-based tool that reaches inside and helps them navigate the cilia themselves.
The researchers found that a bacterial protein known as FhaB carries a built-in region that binds to microtubules, structural components inside cells that help give cilia their shape and motion. Using live imaging, structural biology and infection models, the team showed that this protein is delivered into mammalian cells and is essential for helping the bacteria move from the tips of cilia down to their base, where they are better protected from being swept away. When that protein region was removed, the bacteria were far less able to colonize the respiratory tract.
Christopher S. Hayes, the UC Santa Barbara professor who led the project, pointed to the importance of seeing this process unfold in real time. “The challenge was to figure out what advantage the microtubule-binding domain conferred to Bordetella. Dr. Michael Costello developed a novel microscopy approach that enabled us to visualize bacteria on living, beating cilia in real time. This revealed that interactions with the axoneme are required to penetrate the cilia forest.”
At UC Irvine, researchers helped reveal the physical basis for that interaction in remarkable detail. Shane Gonen, assistant professor of molecular biology and biochemistry, said the visual evidence was compelling from the start. “I have had the fortune to work with microtubules at various stages of my career and I am continually fascinated by their wide-ranging interactions and crucial functional roles in our bodies. We specialize in Cryogenic Electron Microscopy, or CryoEM, where we use imaging to study protein structure and interactions. It was incredible to see the binding of the C-terminal domain of FhaB (FhaB-CT) with microtubules and that it was noticeable even in raw images from the microscope. When we were able to see the proteins at high-resolution, I was further struck by just how extensive the interaction of FhaB-CT was with the alpha subunit, one of the two main repeating subunits of microtubules. This wasn’t a glancing interaction that is likely to break apart easily but an extensive interface over a wide surface area.”
That high-resolution view helped connect molecular structure to biological function. Bryan Neumann, assistant project scientist at UC Irvine, emphasized how powerful it was to link the images directly to what the bacteria were doing in tissue. “The Cryo-EM data gave us an extraordinary, near-atomic-level depiction of this bacterial protein bound to microtubules. Seeing that interaction at roughly 2.4-angstrom resolution and then connecting it directly to how effectively Bordetella overcomes cilia beating to colonize the cellular base makes the story exceptionally compelling.”
Beyond explaining a clever bacterial strategy, the findings also suggest practical next steps. Celia Goulding, UC Irvine professor of molecular biology and biochemistry & pharmaceutical sciences, said the work could eventually help researchers turn the bacteria’s own tactics against them. “The next steps will focus on elucidating the mechanism by which the FhaB-CT domain traverses the microtubule network, enabling Bordetella bacteria to localize to the base of the ciliary forest. It will also be important to identify the human receptor recognized by FhaB, as this interaction could potentially be exploited for targeted delivery of ‘Trojan horse’ antibacterials. Finally, these insights may inform strategies to improve the efficacy of the whooping cough vaccine by incorporating the FhaB-CT domain into existing formulations.”
Those possibilities make the study especially promising. By showing how bacteria overcome one of the body’s most effective natural clearance systems, the research offers a path toward new therapies that could stop colonization earlier, reduce the burden of respiratory disease and help scientists design more precise interventions. It also highlights the value of collaboration across campuses and disciplines, bringing together microbiology, imaging, structural biology and infection research to answer a long-standing question about how pathogens establish themselves in the airways.
The work now invites broader support for continued research into respiratory infections and the basic biology that underlies them. Discoveries like this one do more than solve a scientific puzzle. They create new opportunities to protect public health, improve vaccines and treatments, and strengthen our ability to respond to infectious disease with smarter, more targeted solutions.
About the University of California, Irvine Charlie Dunlop School of Biological Sciences:
Recognized for its pioneering research and academic excellence, the Charlie Dunlop School of Biological Sciences plays a crucial role in the university’s status among the nation’s top 10 public universities, as ranked by U.S. News & World Report. It offers a broad spectrum of degree programs in the biological sciences, fostering innovation and preparing students for leadership in research, education, medicine and industry. Nestled in a globally acclaimed and economically vibrant community, the school contributes to the university’s impact as Orange County’s largest employer and a significant economic contributor. Through its commitment to exploring life’s complexities, the Dunlop School embodies the UC Irvine legacy of innovation and societal impact. For more on the Charlie Dunlop School of Biological Sciences, visit https://www.bio.uci.edu/.