Saliva plays a role in the body's defense against traveler's diarrhea

MARCH 8, 2018, by Boston University School of Medicine
https://medicalxpress.com/news/2018-03-saliva-role-body-defense-diarrhea.html

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Researchers have identified a protein in saliva (histatin-5) that protects the body from traveler's diarrhea.

The findings, available online in the Journal of Infectious Diseases, may lead to the development of new preventive therapies for the disease.

Traveler's diarrhea is an inconvenience to many in the U.S., but worldwide it can be deadly. It produces a watery diarrhea, which can cause life-threatening dehydration in infants or other vulnerable populations in endemic countries. With more than one billion cases each year, hundreds of thousands of deaths can be attributed to this bacterial disease which is caused by enterotoxigenic Escherichia coli (ETEC), invading the small intestine using arm-like structures called "pili."

Researchers from Boston University School of Medicine (BUSM) and collaborators exposed miniature human small intestines that they were able to grow in a dish (organoids) to the bacteria ETEC in the presence and absence of the protein histatin-5. When examined under the microscope, significantly fewer bacteria were able to attach to the tissue in the presence of histatin-5.

"We found that the protein histatin-5 present in human saliva stiffens the pili of ETEC, preventing the bacteria from effectively adhering to the small intestine," explained corresponding author Esther Bullitt, PhD, associate professor of physiology and biophysics at BUSM. "If they can't attach, they simply can't cause disease."

Prior to this study, it was not known that saliva could play such a large role in protecting the body from gut infections. According to the researchers, this initial line of defense in the mouth likely explains why it takes such a large number of ETEC to infect a human. They also suggest that histatin-5 might be manufactured as a dissolvable powder and used to prevent traveler's diarrhea in the future.

This new finding opens up the possibility that other salivary proteins might exist which protect against many other diseases, including infectious gastritis, food poisoning or even pneumonia. "We believe that our data represent the first example of a new paradigm in innate immunity: the contributions of salivary components to preventing infection. This research opens an untapped avenue for prevention of enteric infectious diseases through the targeted use of naturally occurring components of saliva."

Researchers determine bacteria structure responsible for traveler's diarrhea

JULY 10, 2019, by Boston University School of Medicine

https://medicalxpress.com/news/2019-07-bacteria-responsible-diarrhea.html


Overall reconstruction of CFA/I pili. (a) Side view of the CFA/I pilus reconstruction fit with the model, with subunits colored distinctively. (b) A representative outer region of the CFA/I pilus structure, Pro13 is highlighted in red. (c) The cut-away view shows core of CFA/I pilus rod, where the N-terminal extension of subunit n is inserted into the β-strands groove of the preceding subunit. A close-up view shows the clearly separated β-strands as well as the Pro13 at the end of N-terminal extension of each subunit. (d) A view of Pro13 shown in stick representation within the cryo-EM map. 

For the first time researchers have deciphered the near-atomic structure of filaments, called 'pili', that extend from the surface of bacteria that cause traveler's diarrhea. Without pili, these bacteria do not cause disease. Knowing this structural information may lead to the development of new preventive therapies for the disease.

Traveler's is an inconvenience to many in the U.S., but worldwide it can be deadly. It produces a watery diarrhea, which can cause life-threatening dehydration in infants or other vulnerable populations. With more than one billion cases each year, hundreds of thousands of deaths can be attributed to this bacterial disease which is caused by enterotoxigenic Escherichia coli (ETEC), invading the small intestine via pili.

Researchers from Boston University School of Medicine (BUSM), University of Virginia and Umeå University used heat to remove the pili from the
"We anticipate that our new, detailed knowledge of the structure of pili will help in developing vaccines and drugs to prevent and treat traveler's diarrhea. In particular we are excited about a peptide found in saliva that can disrupt unwinding and/or rewinding of pili as a means of inhibiting bacterial adhesion and explained corresponding author Esther Bullitt, Ph.D., associate professor of physiology and biophysics at BUSM.



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