Revealing the structural basis underpinning the biophysical properties of pili

According to the World Health Organization, enterotoxigenic Escherichia coli (ETEC) bacteria are the most common cause of traveler’s diarrhea and cause the greatest number of known community-acquired cases of childhood diarrhea in the developing world. While this is only an annoyance in adults, it can lead to chronic malnutrition, stunted growth, and reduced cognitive function in newborns and young children.

ETEC attaches to host intestinal epithelia by long, thin filaments known as “pili,” an early and important step in diarrhea pathogenesis. These fibers are required for ETEC infection to begin in the intestines.

Scientists have observed that pili are fine-tuned for their chosen microenvironment, like the gut or the urinary tract. They also discovered that some use short loops to link to one another. Others employ long extensions to reach a far distance. This discovery has significant implications for developing improved treatments for diarrheal diseases.

Unwinding (and rewinding) of pili reduces the force at the site of binding and allows the bacteria to stay attached. Because pili are critical for bacteria to cause disease, finding a way to prevent pili from unwinding and rewinding can be used in the future to prevent diarrheal disease.”

Esther Bullitt, Study Corresponding Author and Associate Professor, Physiology & Biophysics, Boston University Chobanian & Avedisian School of Medicine

The investigators utilized a combination of approaches, including a cryogenic electron microscope to image the pili in a near-native state, lasers to pull on the pili and quantify the force required to unwind them, and computer simulations to view the unwinding at the atomic level.

Investigators are exploring strategies to specifically target disease-causing bacteria since pili on different types of bacteria are adjusted for their environment.

Therapeutics that disrupt pili and allow bacteria to be washed away have advantages over current antibiotics, as physical removal would not lead to the evolution of resistant strains and only the pathogens would be targeted, while leaving the ‘good’ bacteria of the microbiome intact.”

Esther Bullitt, Study Corresponding Author and Associate Professor, Physiology & Biophysics, Boston University Chobanian & Avedisian School of Medicine