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UTSW researchers discover how food-poisoning bacteria infect the intestines

Findings revealing efficient assembly of virulence machine could lead to development of treatments for diseases caused by gut pathogens

DALLAS – April 20, 2023 – Researchers at UT Southwestern Medical Center have discovered how a bacterium that infects people after they eat raw or undercooked shellfish creates syringe-like structures to inject its toxins into intestinal cells. The findings, published in Nature Communications, could lead to new ways to treat food poisoning caused by Vibrio parahaemolyticus.

Kim Orth, Ph.D.
Kim Orth, Ph.D., is a Howard Hughes Medical Institute Investigator, a member of the National Academy of Sciences, and a W.W. Caruth, Jr. Scholar in Biomedical Research, and holds the Earl A. Forsythe Chair in Biomedical Science.

“We have provided the first visual evidence of how a gut bacterial pathogen uses this assembly method to build a syringe to deliver a lethal injection to intestinal cells,” said Kim Orth, Ph.D., Professor of Molecular Biology and Biochemistry, a Howard Hughes Medical Institute Investigator, and a W.W. Caruth, Jr. Scholar in Biomedical Research at UTSW. “This work provides a new view of how enteric bacteria when exposed to bile acids efficiently respond and build a virulence system.”

V. parahaemolyticus, commonly found in warm coastal waters, is a leading cause of seafood-related food poisoning. People infected often have diarrhea, cramping, vomiting, fever, and chills.

Researchers knew that V. parahaemolyticus injects molecules into human cells using a structure called the type III secretion system 2 (T3SS2). However, these syringes, composed of 19 different proteins, are not produced or assembled until the bacteria are inside the intestines. Scientists were not sure exactly how this occurs.

The latest findings build on the work of a previous study by the Orth lab.  Dr. Orth and her colleagues tagged components of the V. parahaemolyticus T3SS2 with fluorescent markers and used super-resolution microscopy to track their locations as the bacteria were grown in different conditions. The researchers discovered that when V. parahaemolyticus is exposed to bile acids – digestive molecules in the intestines – the bacteria move DNA containing the T3SS2 genes close to their membrane.

Then, at the exact site where the T3SS2 is needed, V. parahaemolyticus transcribes that DNA into RNA, translates the RNA into protein, and assembles the components of the T3SS2 through the membrane in a process known as transertion. “It is like watching the assembly of a factory that produces a large molecular machine within an hour,” Dr. Orth said. 

These steps were previously thought to occur in more disparate locations around a cell, but pulling the machinery together into one place on the bacterium’s membrane likely helps V. parahaemolyticus more quickly and efficiently build the T3SS2 and infect cells. Since other disease-causing gut bacteria contain molecular components similar to V. parahaemolyticus, the phenomenon of transertion may be widely used, the researchers hypothesize.

Karan Kaval, Ph.D.
Karan Kaval, Ph.D., a UTSW research specialist and member of the Orth lab, was first author of the study.

“Our findings imply that other gastrointestinal pathogens may also use this mechanism to mediate efficient assembly of complex molecular machines in response to environmental cues,” said UTSW research specialist Karan Kaval, Ph.D., first author of the paper.

More work is needed to know which bacteria use transertion to build their T3SS structures and whether drugs could be developed that block transertion to treat V. parahaemolyticus infections.

UTSW researcher Jananee Jaishankar also contributed to this study.

Dr. Orth holds the Earl A. Forsythe Chair in Biomedical Science and is a member of the National Academy of Sciences.

The study was supported by The Welch Foundation (I-1561), the Once Upon a Time Foundation, and the National Institutes of Health (R35 GM134945, R35 GM128674, 1S10OD021685-01A1).

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 24 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.