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 Dissolving protein traffic jam at the entrance of mitochondria
23.05.2019 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Producing tissue and organs through lithography
23.05.2019 | Goethe-Universität Frankfurt am Main

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The geometry of an electron determined for the first time

Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.

The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...

Im Focus: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

Im Focus: A step towards probabilistic computing

Working group led by physicist Professor Ulrich Nowak at the University of Konstanz, in collaboration with a team of physicists from Johannes Gutenberg University Mainz, demonstrates how skyrmions can be used for the computer concepts of the future

When it comes to performing a calculation destined to arrive at an exact result, humans are hopelessly inferior to the computer. In other areas, humans are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Plumbene, graphene's latest cousin, realized on the 'nano water cube'

23.05.2019 | Materials Sciences

New flatland material: Physicists obtain quasi-2D gold

23.05.2019 | Materials Sciences

New Boost for ToCoTronics

23.05.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>