Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bad news for pathogenic bacteria: Scientists find protein essential for bacterial survival

06.08.2004


Further investigation into how the common organism Escherichia coli regulates gene expression has given scientists new ideas for designing antibiotics that might drastically reduce a bacterium’s ability to resist drugs.


A transmission electron micrograph of Escherichia coli (E.coli). (Image -- New York State Department of Health)



The findings, reported in the current issue of the journal Cell, suggest that bacteria rely on a key protein in order to properly regulate gene expression -- a process fundamental to cell survival. This protein, called DksA, coordinates the expression of numerous genes in response to environmental signals.

Figuring out how to block DksA production in harmful bacteria may help scientists develop antibiotics that these bacteria are less likely to resist, said Irina Artsimovitch, a study co-author and an assistant professor of microbiology at Ohio State University.


The current study suggests that DksA is the glue that holds together two key components of bacterial gene expression – a molecule called ppGpp and an enzyme called RNA polymerase. RNA polymerase carries out transcription, the first step in gene expression.

In recent work, Artsimovitch and her colleagues discovered that ppGpp regulates gene expression by controlling amino acid production in bacteria. A cell makes ppGpp when amino acid levels are low, and ppGpp tells a cell to go dormant until amino acid levels return to normal.

"But there was something missing from the ppGpp story," Artsimovitch said. "We knew that ppGpp had a dramatic effect on gene expression, but for some reason that effect was drastically decreased when we conducted experiments in the laboratory."

Work by other researchers had suggested a link between DksA and the ppGpp-initiated stress response in the cell. But scientists couldn’t agree on what role, if any, DksA played in the effect of ppGpp on gene expression.

Working with a team of researchers led by Dmitry Vassylyev, a scientist with the RIKEN research institution in Japan, Artsimovitch and Ohio State microbiologist Vladimir Svetlov solved high-resolution crystal structures of DksA.

Solving this structure meant that the researchers could at last determine just how DksA helped ppGpp hold fast to its target, RNA polymerase.

DksA uses something scientists call the "backdoor of gene expression," a cavity on the RNA polymerase molecule called the secondary channel. DksA squeezes through this narrow tunnel toward the site where ppGpp binds to the enzyme. Once here, the protein helps ppGpp stay bound to RNA polymerase.

"The secondary channel seems to be the hotspot for many interactions," Artsimovitch said. "It leads straight to the active site, and presents a confined area where many proteins and antibiotics that control transcription may bind to carry out their business."

Knowing what roles ppGpp and DksA play in how bacteria respond to stress and other physiological stimuli may help scientists create new antibacterial drugs that target mechanisms specific and unique to harmful bacteria.

"Conventional antibiotics aimed at killing bacteria also put immense pressure on bacteria to survive, and to ultimately develop resistance to these drugs," Artsimovitch said. "Forcing harmful bacteria into a stationary state by controlling ppGpp levels may be the way to circumvent the rise in antibiotic resistance.

"ppGpp and DksA are found in all bacteria, including harmful ones," she continued. "Using ppGpp-based compounds to shut down gene expression in harmful bacteria could help curb the spread of infections."

Grants from the National Institutes of Health and from RIKEN supported this research.

Artsimovitch, Vassylyev and Svetlov conducted the study with Anna Perederina, Marina Vassylyeva, Tahir Tahirov and Shigeyuki Yokoyama, all with RIKEN.

Irina Artsimovitch | EurekAlert!
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht Embryonic development: How do limbs develop from cells?
18.05.2018 | Humboldt-Universität zu Berlin

nachricht Reading histone modifications, an oncoprotein is modified in return
18.05.2018 | American Society for Biochemistry and Molecular Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>