Vibrio parahaemolyticus bacteria, which cause gastroenteritis, inject proteins called effectors into host cells. One of those effectors, VopQ, almost immediately starts to disrupt the important process of autophagy via a novel channel-forming mechanism, the scientists report in the investigation available online at the Proceedings of the National Academy of Sciences.
Autophagy is the cellular housekeeping mechanism used to recycle nutrients in cells as well as to fight off pathogens. The term autophagy comes from the Greek words for self and eating. During the process, nutrients are recycled by the lysosome, an internal organelle, to produce metabolites that can be used by the cell.
“Our study identifies a bacterial effector that creates gated ion channels and reveals a novel mechanism that may regulate autophagy,” said Dr. Kim Orth, professor of molecular biology and biochemistry. She is a corresponding author on the published study. The first author is Anju Sreelatha, a graduate student in Dr. Orth’s laboratory.
“Disruptions of autophagic pathways are implicated in many human diseases, including neurodegenerative disease, liver disease, some cancers, and cardiomyopathy (heart muscle disease),” Ms. Sreelatha said.
She explained that ion channels are pores in the membranes of cells or of organelles within cells that allow regulated passage of small molecules or ions across membranes. Gated channels have a mechanism that opens and closes them, making these proteins potential targets for drug development.
“The identification of a channel that opens and closes and thereby affects autophagy may give us a handle by which to modulate this important process,” she said, adding that the researchers found that VopQ’s channel activity turned off autophagy.
“During infection, VopQ is injected into the host cell where the protein binds to a lysosomal membrane protein and forms small pores, all within minutes of infection. The resulting complex of proteins causes ions to leak and the lysosomes to de-acidify. Lacking acidification, lysosomes cannot degrade the unneeded cellular components and autophagy is disrupted,” Ms. Sreelatha said.
Dr. Orth said “Bacterial pathogens have evolved a number of ways to target and manipulate host cell signaling; the ability of VopQ to form a gated ion channel and to inhibit autophagy represents a novel mechanism.”
Further characterization of the mechanism by which VopQ sabotages cells to disrupt autophagy may lead to a better understanding of host-pathogen interactions as well as advance our understanding of the pathway, eventually leading to new treatments for diseases in which autophagy has gone awry, they noted.
Other UT Southwestern scientists involved were Dr. Hui Zheng, a postdoctoral researcher of cell biology, and Dr. Qiu-Xing Jiang, assistant professor of cell biology. Also participating were Terry Bennett and Dr. Vincent Starai of the University of Georgia.
Funding was provided by the National Institute of Allergy and Infectious Diseases; the Burroughs Wellcome Foundation; the Welch Foundation; the National Institute of General Medical Sciences; the Cancer Prevention and Research Institute of Texas; and by University of Georgia Startup Funds.About UT Southwestern Medical Center
Deborah Wormser | Newswise
Microgel powder fights infection and helps wounds heal
14.11.2018 | Michigan Technological University
Spread of deadly eye cancer halted in cells and animals
13.11.2018 | Johns Hopkins Medicine
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Physics and Astronomy
16.11.2018 | Life Sciences
15.11.2018 | Earth Sciences