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Study Reveals Mechanisms that Bacteria Use in Surface Sensing

Findings from a new Dartmouth-led study published in mBio, involving researchers from Dartmouth’s Geisel School of Medicine, the University of California Los Angeles, and Catholic University in Belgium, reveal key mechanisms that allow bacteria to sense contact with surfaces and begin biofilm formation.

Opportunistic pathogens like Pseudomonas aeruginosa are made up of genetically identical bacterial cells that can form biofilms or colonies on both non-living surfaces (such as medical implants and catheter lines) and living surfaces (such as airway cells in diseases like cystic fibrosis). These pathogens are often highly tolerant to antibiotics, causing infections that can be harmful or even deadly to patients.

Shanice Webster, PhD. Photo: Yuti Cheng

“For some time, we’ve been focused on trying to understand how these microbes go from swimming around in a liquid environment as individual cells to choosing a surface that is conducive to their growth and forming these big, complex communities,” says George O’Toole, PhD, the Elmer R. Pfefferkorn, PhD, Professor of Microbiology and Immunology at Dartmouth’s Geisel School of Medicine and senior author on the study. The lead author of the study is Shanice Webster, PhD, a former graduate student in the O’Toole Lab at Dartmouth who is now doing her post-doctoral studies at Duke University.

For nearly a decade, says O’Toole, researchers have been speculating that bacteria use the sense of touch, what’s known as “mechanosensation,” to detect when they’ve made contact with a surface—but the mechanisms involved have been poorly understood.

Using a combination of tools—including molecular genetics and single-cell analysis, with biophysical, biochemical, and genomics techniques—the investigators discovered that a protein known as PilY1, which is a protein located at the tip of the type IV pili in Pseudomonas aeruginosa, plays a key role in the mechanosensation process.

“The protein we identified, PilY1, is part of a kind of cellular appendage called a pilus, which you can think of as a long, rod-shaped protein filament protruding from the cell,” he explains.

“We were able to show that when PilY1 senses the physical force of contact, it changes its shape, triggering a number of downstream signaling events inside the cell—including that the cell stops moving and starts producing secreted sugars that help the bacteria stick to the surface and to each other. So, it turns on all of the pathway factors needed to adapt to a surface lifestyle,” says O’Toole, who in previous work with colleagues has identified other components of the signaling pathway

In perhaps the most surprising finding of the study, the research team discovered that the PilY1 protein shares features with a protein found in humans known as the von Willebrand factor.

“It’s a mechanosensitive protein that’s involved in blood clotting that undergoes changes in response to force. And there are other examples of these mechanosensitive proteins, as well, such as titin, which is a protein in our muscles,” he says. “For me, one of the most exciting parts of the work we’ve done here is being able to draw this analogy to what people have been studying for a long time in eukaryotic systems.”

The study was supported by the NIH, COBRE/National Institute of General Medical Sciences, the NSF Graduate Research Fellowship, BioMT through NIH/NIGMS, the Excellence of Science-EOS program, the European Research Council, and the National Fund for Scientific Research.

Founded in 1797, the Geisel School of Medicine at Dartmouth strives to improve the lives of the communities it serves through excellence in learning, discovery, and healing. The Geisel School of Medicine is renowned for its leadership in medical education, healthcare policy and delivery science, biomedical research, global health, and in creating innovations that improve lives worldwide. As one of America’s leading medical schools, Dartmouth’s Geisel School of Medicine is committed to training new generations of diverse leaders who will help solve our most vexing challenges in healthcare.