the Yersinia bacteria, known to cause plague and gastroenteritis, contain a small molecule, called a virulence factor, that the researchers have found modifies host enzymes critical to normal functioning.
"This type of modification has never been seen in cells and presents a new paradigm for how cells may regulate signaling," said Dr. Kim Orth, assistant professor of molecular biology and senior author of the study appearing in the May 26 edition of Science.
"Yersinia is a nasty pathogen that uses an arsenal of virulence factors to cause disease," she said.
When a cell is infected with a bacterial pathogen, it activates a chain of reactions involving enzymes. One enzyme adds a group of atoms containing phosphorus — called a phosphate group — to another enzyme, a process called phosphorylation, which spurs that enzyme to add a phosphate group to yet another enzyme, and so on. These "cascading" events trigger an appropriate immune response.
Yersinia, however, has the ability to prevent its host from mounting the response, enabling the bacteria to survive and multiply.
The researchers found that one of the Yersinia outer proteins, called YopJ, cripples these cascades by adding a small molecule called an acetyl group to two key sites on a host enzyme where the phosphate groups are usually added.
Because the host’s enzymes are modified by acetyl groups, they can no longer be activated by phosphate groups, and the enzymatic cascade critical for triggering an innate immune response is not activated.
The internal signaling that YopJ affects is common to many species, from yeast to mammals. In addition, other pathogens that attack animals and plants use proteins that are similar to YopJ.
The research is not geared toward finding a cure for plague, which affects about a dozen people in the United States a year and is treatable with antibiotics. Instead, the scientists are working to find out how the pathogen disrupts the immune system and to understand the machinery critical for stimulating an immune response.
"There are many virulence factors used by bacterial pathogens to co-opt the host signaling molecules," Dr. Orth said. "These virulence factors affect central signaling machinery, and we want to understand how they are doing it."
Understanding the relationship between the pathogens and the hosts will help researchers uncover critical steps in how host cells normally operate, Dr. Orth said.
"The next step is to see whether the addition of acetyl groups to key sites on enzymes during cellular signaling is normal for animal and plant cells, and if so, under what circumstances," said Dr. Orth.
Other UT Southwestern researchers involved in the study were first author Sohini Mukherjee, student research assistant in molecular biology; Gladys Keitany, research assistant in molecular biology; Dr. Yan Li, instructor of biochemistry; Yong Wang, research assistant in molecular biology; Dr. Haydn Ball, assistant professor of biochemistry; and Dr. Elizabeth Goldsmith, professor of biochemistry.
The work was supported by the National Institute of Allergy and Infectious Diseases, the Beckman Foundation and the Welch Foundation.
Aline McKenzie | EurekAlert!
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences