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
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 90,000 hospitalized patients and oversee more than 1.9 million outpatient visits a year.
This news release is available on our home page at http://www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via email, subscribe at http://www.utsouthwestern.edu/receivenews
Deborah Wormser | EurekAlert!
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
26.04.2017 | Life Sciences
26.04.2017 | Physics and Astronomy
26.04.2017 | Earth Sciences