Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Salmonella stays deadly with a 'beta' version of cell behavior

15.08.2011
Salmonella cells have hijacked the protein-building process to maintain their ability to cause illness, new research suggests.

Scientists say that these bacteria have modified what has long been considered typical cell behavior by using a beta form of an amino acid – as opposed to an alpha form – during the act of making proteins.

Beta versions of amino acids occur in nature under rare and specific circumstances, but have never been observed as part of protein synthesis. Before this finding, in fact, researchers had determined that virtually all proteins were constructed with the alpha forms of amino acids.

This work has shown that when researchers delete any one of three genes from the process that makes use of the beta form of the amino acid, or if they insert the alpha form in the beta version's place, Salmonella cells are no longer able to cause disease. The amino acid in question is lysine, one of 22 genetically encoded amino acids that are strung together in cells to make proteins.

"When these genes were knocked out, the cells became sensitive to antibiotics. And if we put beta lysine into the medium where cells were growing, they became resistant to antibiotics," said Michael Ibba, professor of microbiology at Ohio State University and a senior author of the study. "So we could see the beta amino acid being taken up and used. The cells really do need the beta amino acid to be resistant to antibiotics, and for other aspects of their virulence."

This finding suggests that the process using this specific beta amino acid could be an attractive antibiotic target for this common pathogen, the researchers say.

The Centers for Disease Control and Prevention estimates that about 1.4 million people in the United States are infected with Salmonella each year, though only 40,000 cases are reported. Most people infected with Salmonella develop diarrhea, fever and abdominal cramps. Though recovery can occur within a week without treatment, some severe cases require antibiotic treatment and hospitalization.

The study is published in the Aug. 14 online edition of the journal Nature Chemical Biology.

This work began when University of Toronto scientists exploring the origins of Salmonella's virulence identified three genes that were clear players in the process. These three genes – called YjeK, PoxA and EF-P – were unusual in this context.

Genes that confer virulence in bacteria typically have a specific job, such as producing toxins or transporters. But these three virulence genes all looked like they should have a role in the protein synthesis machinery – which is Ibba's expertise.

Under normal circumstances in cells, an enzyme will select amino acids in the cell and place them on a molecule called transfer RNA, or tRNA, which leads to translation of the genetic code into proteins.

In Salmonella cells, these steps are similar, but with a few surprising twists, Ibba said. He and colleagues confirmed that the YjeK gene makes beta lysine, and showed that the PoxA gene takes that beta lysine and attaches it to EF-P – a protein that partially mimics the shape and function of tRNA.

"It's a really unexpected pathway," said Ibba, also an investigator in Ohio State's Center for RNA Biology. "It is a mimic of what normally makes protein in a cell. Where a cell would normally be expected to use an alpha amino acid, Salmonella puts on a beta amino acid. And it ends up making molecules that lead to the cells being virulent."

The research team first reconstructed this unusual protein synthesis process in test tube experiments, and then followed with studies in cell cultures. Even before they took on studying the mechanism, however, they knew that the effects of these virulence genes were powerful: In earlier animal studies, deleting any one of the three genes and then infecting mice with these altered Salmonella cellshad no effect on the animals. When the genes were left intact and cells were injected into mice, the resulting Salmonella infection killed the animals.

In addition, when the researchers tricked Salmonella cells into using alpha lysine for this pathway instead of beta lysine, the cells lost their ability to cause illness.

"This tells us the cell is not going to be able to easily replace the beta amino acid," Ibba said. "It is essential for virulence in Salmonella."

And that, he said, is why that amino acid might be such an effective drug target, especially as humans don't seem to make beta amino acids at all. "You have to make an antibiotic look like something natural, only different. If you have something that's already different like a beta amino acid, you've potentially got a much better drug target because it involves chemistry that's comparatively rare in the cell. It's harder for the cell to try to alter its own chemistry to develop resistance," Ibba said.

From here, the researchers are observing cell behavior later in the protein-building process to figure out how this hijacked system actually gives Salmonella its virulence.

This work is supported by the National Institutes of Health, the Canada Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and Ohio State.

Co-authors include Hervé Roy, a former Ohio State research scientist now at the University of Central Florida; S. Betty Zou and William Navarre of the University of Toronto; Tammy Bullwinkle of Ohio State's Department of Microbiology; and Benjamin Wolfe and Craig Forsyth of Ohio State's Department of Chemistry.

Contact: Michael Ibba, (614) 292-2120; Ibba.1@osu.edu
Written by Emily Caldwell, (614) 292-8310; Caldwell.151@osu.edu

Michael Ibba | EurekAlert!
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences

nachricht The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>